An fMRI study of the Trail Making Test

This study investigated the cerebral correlates of the Trail Making Test (TMT), used commonly as a measure of frontal lobe function. Such work sheds additional light on the known shortcomings of the TMT as a localizing instrument, as indicated, for example, by studies of patients with focal brain lesions. Functional magnetic resonance imaging (fMRI) was used to record brain activity while participants performed the TMT using a custom-built, fiber-optic fMRI-compatible writing device, the "virtual stylus". Unlike in a previous fMRI study that used a verbal adaptation of the TMT, the virtual stylus enabled a closer depiction of the brain regions engaged by the actual paper-and-pencil task. Twelve, right-handed healthy young adults participated. In Part A of the task, participants were required to link in ascending order numbers (1-2-3 ...) that were randomly distributed on a computer screen. In Part B, participants were required to link alternately between numbers and letters (1-A-2-B ...). Although behavioral performance was somewhat less than typically obtained with the TMT due to use of the virtual stylus, distinct left-sided dorsolateral and medial frontal activity was revealed when comparing Part B versus Part A. These findings agree with existing literature showing sensitivity of the TMT to frontal regions in the left hemisphere. However, other activity was also observed (left middle and superior temporal gyrus) reinforcing that the brain-behavior correlations for the TMT are multifaceted and not restricted to the frontal lobe.     

The Relationship Between Gray Matter Morphometry and Neuropsychological Performance in a Large Sample of Cognitively Healthy Adults

Voxel-based morphometry (VBM) was used to examine the relationship between gray matter (GM) volume and performance on two commonly used clinical neuropsychological measures of frontal lobe or executive function, the Trail Making Test part B (TrailsB) and the Controlled Oral Word Association Test (COWAT) in 221 cognitively healthy adults between the ages of 18 and 84. We hypothesized that these measures would be associated with GM volume in the dorsolateral frontal lobes. Voxel-based multiple regression was used to correlate cognitive function with modulated GM probability maps while controlling for age, education, gender, and total intracranial volume. A relationship with TrailsB was found in bilateral lateral inferior frontal gyri and left basal ganglia. A relationship with COWAT was found in the left lateral inferior and middle frontal gyri. Lesion studies have long implicated the importance of these regions for executive function. The present results confirm and extend those prior findings to healthy adults.     

Pathways to similar executive impairment: Comparison of schizophrenia patients and healthy aging individuals

Executive impairment is prominent in schizophrenia, in conditions such as Parkinson's disease and dementia and in healthy aging. Identifying processes that critically constrain executive function can advance investigation of their biological basis and treatment planning. Recent findings that elderly healthy individuals showed similar impairment on conditional exclusion task as schizophrenia patients raised the question whether similar processes are impaired. To test this we compared 56 schizophrenia patients, 57 elderly and 77 young healthy individuals on three executive tests: conditional exclusion, abstraction and inhibition and tests of working memory and psychomotor speed. Schizophrenia patients performed worse than elderly healthy on abstraction, inhibition and verbal working memory. They were similarly impaired on Penn Conditional Exclusion Test (PCET) outcome measures but differed in performance characteristics. Schizophrenia patients needed relatively more trials to learn the first PCET category than the second or the third. This correlated with other cognitive impairments, particularly in working memory. Elderly healthy individuals found it most difficult to learn the last category. The two groups showed different error patterns. We propose that schizophrenia patients have particular difficulty in early (probabilistic) learning (“what to do”) while aging individuals have selective impairment in executive integration. These constitute distinct targets for customized treatment in the two conditions.     

A preliminary examination of gut microbiota,sleep, and cognitive flexibility in healthy older adults

ObjectivesInadequate sleep increases the risk for age-related cognitive decline and recent work suggests a possible role of the gut microbiota in this phenomenon. Partial sleep deprivation alters the human gut microbiome, and its composition is associated with cognitive flexibility in animal models. Given these findings, we examined the possible relationship among the gut microbiome, sleep quality, and cognitive flexibility in a sample of healthy older adults.MethodsThirty-seven participants (age 64.59 ± 7.54 years) provided a stool sample for gut microbial sequencing and completed the Pittsburgh Sleep Quality Index and Stroop Color Word Test as part of a larger project.ResultsBetter sleep quality was associated with better Stroop performance and higher proportions of the gut microbial phyla Verrucomicrobia and Lentisphaerae. Stroop Word and Color-Word performance correlated with higher proportions of Verrucomicrobia and Lentisphaerae. Partial correlations suggested that the relationship between Lentisphaerae and Stroop Color-Word performance was better accounted for by sleep quality; sleep quality remained a significant predictor of Color-Word performance, independent of the Lentisphaerae proportion, while the relationship between Lentisphaerae and Stroop performance was non-significant. Verrucomicrobia and sleep quality were not associated with Stroop Word performance independent of one another.ConclusionsThe current findings suggest a possible relationship among sleep quality, composition of the gut microbiome, and cognitive flexibility in healthy older adults. Prospective and experimental studies are needed to confirm these findings and determine whether improving microbiome health may buffer against sleep-related cognitive decline in older adults.     

Response inhibition is associated with white matter microstructure in children

Cognitive control of thoughts, actions and emotions is important for normal behaviour and the development of such control continues throughout childhood and adolescence. Several lines of evidence suggest that response inhibition is primarily mediated by a right-lateralized network involving inferior frontal gyrus (IFG), presupplementary motor cortex (preSMA), and subthalamic nucleus. Though the brain's fibre tracts are known to develop during childhood, little is known about how fibre tract development within this network relates to developing behavioural control. Here we examined the relationship between response inhibition, as measured with the stop-signal task, and indices of regional white matter microstructure in typically-developing children. We hypothesized that better response inhibition performance would be associated with higher fractional anisotropy (FA) in fibre tracts within right IFG and preSMA after controlling for age. Mean FA and diffusivity values were extracted from right and left IFG and preSMA. As hypothesized, faster response inhibition was significantly associated with higher FA and lower perpendicular diffusivity in both the right IFG and the right preSMA, possibly reflecting faster speed of neural conduction within more densely packed or better myelinated fibre tracts. Moreover, both of these effects remained significant after controlling for age and whole brain estimates of these DTI parameters. Interestingly, right IFG and preSMA FA contributed additively to the prediction of performance variability. Observed associations may be related to variation in phase of maturation, to activity-dependent alterations in the network subserving response inhibition, or to stable individual differences in underlying neural system connectivity.     

Thalamic structures and associated cognitive functions: Relations with age and aging

The thalamus, with its cortical, subcortical, and cerebellar connections, is a critical node in networks supporting cognitive functions known to decline in normal aging, including component processes of memory and executive functions of attention and information processing. The macrostructure, microstructure, and neural connectivity of the thalamus changes across the adult lifespan. Structural and functional magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) have demonstrated, regional thalamic volume shrinkage and microstructural degradation, with anterior regions generally more compromised than posterior regions. The integrity of selective thalamic nuclei and projections decline with advancing age, particularly those in thalamofrontal, thalamoparietal, and thalamolimbic networks. This review presents studies that assess the relations between age and aging and the structure, function, and connectivity of the thalamus and associated neural networks and focuses on their relations with processes of attention, speed of information processing, and working and episodic memory.     

Executive Function in Preschoolers with Autism: Evidence Consistent with a Secondary Deficit

Recent research on executive function (EF) deficits in autism has led investigators to conclude that EF deficits are secondary to the disorder. The current study has two major goals: (1) Examine whether specific EF deficits are present in the youngest autism group to date (mean = 2.9 years), and (2) examine whether such deficits are secondary to autism, or act as an early non-specific cognitive risk factor for autism by comparing EF abilities of this autism group to a CA-matched typically developing group. Results from Experiment 1 suggest no specific EF deficits in autism relative to MA-matched controls, while results from Experiment 2 are consistent with the hypothesis that EF deficits may emerge as a secondary deficit in autism. Alternative hypotheses are also considered.     

额叶癫(癎)执行功能损害及磁共振弥散张量成像研究

目的用磁共振弥散张量成像技术研究额叶癫患者执行功能损害的相关脑区及病理改变,探讨其可能的发生机制。方法对32例成人额叶癫患者和75例正常健康对照者进行神经心理检查,并对18例常规影像无病灶的额叶癫患者和20例正常健康对照者进行弥散张量成像扫描及统计分析。结果额叶癫患者组语义流畅性明显差于对照组,数字广度测验得分和90min正确填写数字符号个数明显低于对照组。与对照组比较,额叶癫患者右侧额叶MD值明显高于对照组;右侧外囊、尾状核和双侧丘脑的FA值明显低于对照组,差异具有显著性意义。相关分析显示双侧内囊前肢、左侧外囊、左枕叶皮质下白质FA值与语义流畅性呈正相关。左侧内囊膝部、内囊后肢和丘脑MD值与MMSE呈负相关;双侧内囊前肢、左侧外囊、额叶、枕叶相应白质内FA值与MMSE呈正相关。结论DTI显示额叶癫患者右侧额叶MD值明显增高、右侧外囊、尾状核和双侧丘脑的FA值明显减低,提示额叶癫患者在上述区域可能存在细微病理改变,执行功能可能超出前额叶的范围。     

Gray matter alteration in dyslexia: converging evidence from volumetric and voxel-by-voxel MRI analyses

Affecting up to 4-10% of the population, dyslexia is a highly prevalent, childhood onset developmental disorder adversely influencing multiple domains of adaptive functioning throughout the lifespan. The present brain imaging study was conducted in order to investigate the neuroanatomical correlates of developmental dyslexia. The MRI brain scans of 10 males with dyslexia and 14 matched controls were analyzed with (1) a classical volumetric method measuring gray and white matter lobar volumes and (2) a voxel-by-voxel method. The voxel-by-voxel method identifies changes in tissue density and localizes morphologic alterations without limiting the analyses to predefined regions. Subsequent correlations between gray matter density and neuropsychological performance on specific phonological processing tasks (rhyme judgment) were conducted. Volumetric analyses revealed significantly reduced gray matter volumes in both temporal lobes in dyslexic individuals. The voxel-by-voxel analyses further localized changes to the left temporal lobe, revealing reduced gray matter density in the middle and inferior temporal gyri. Conversely, increased gray matter density was found in the precentral gyri bilaterally. As a combined group, the dyslexic and control subjects demonstrated positive correlations between performance on the rhyme judgment tasks and gray matter density in the middle and inferior frontal gyri, and the middle temporal gyri bilaterally. The current study indicates that dyslexia is associated with a structural gray matter deficit involving a complex fronto-temporal network implicated in phonological processing.     

White matter volume predicts reaction time instability

Information processing speed is a central concept in cognitive psychology and neuropsychology. Previous studies have mostly focused on mean reaction time (RT), and largely ignored intra-individual differences (the standard deviation of the RT: sdRT). Still, intra-individual inconsistency across trials has been shown to correlate with age, neurological disorders, intelligence, and performance on cognitive tests. However, sdRT has not been correlated with neuroanatomical variables. Such knowledge is important to the understanding of the neurobiological foundation for intra-individual variability. In the present study, white matter (WM) and cortical gray matter (GM) volume obtained from the average of two MR scans of 71 healthy participants (aged 20-88 years) were correlated with sdRT and mean RT obtained from a 3-stimulus visual oddball task. Negative correlations were hypothesized between sdRT and WM and between mean RT and cortical GM volume. These hypotheses were confirmed. The correlation between sdRT and WM volume was significant also independently of effects of age, gender, and mean RT, while there was a trend towards a significant correlation (p=.085) between cortical GM volume and mean RT independently of age. A path model was constructed, showing that age and sdRT gave independent contributions to the variance in performance intelligence, and that WM volume predicted performance score through the influence of sdRT. Further, sdRT was a stronger predictor of performance intelligence than mean RT. It is concluded that sdRT and mean RT may have different neuroanatomical correlates, and that sdRT is related to WM characteristics of the brain.     

White matter tract integrity in aging and Alzheimer's disease

The pattern of degenerative changes in the brain white matter (WM) in aging, mild cognitive impairment (MCI), and Alzheimer's disease (AD) has been under debate. Methods of image analysis are an important factor affecting the outcomes of various studies. Here we used diffusion tensor imaging (DTI) to obtain fractional anisotropy (FA) measures of the WM in healthy young (n = 8), healthy elderly (n = 22), MCI (n = 8), and AD patients (n = 16). We then applied "tract-based spatial statistics" (TBSS) to study the effects of aging, MCI, and AD on WM integrity. Our results show that changes in WM integrity (that is, decreases in FA) are different between healthy aging and AD: in healthy older subjects compared with healthy young subjects decreased FA was primarily observed in frontal, parietal, and subcortical areas whereas in AD, compared with healthy older subjects, decreased FA was only observed in the left anterior temporal lobe. This different pattern of decreased anatomical connectivity in normal aging and AD suggests that AD is not merely accelerated aging.     

The neural correlates of visuo-spatial working memory in children with autism spectrum disorder: effects of cognitive load

Background

Research on the neural bases of cognitive deficits in autism spectrum disorder (ASD) has shown that working memory (WM) difficulties are associated with abnormalities in the prefrontal cortex. However, cognitive load impacts these findings, and no studies have examined the relation between WM load and neural underpinnings in children with ASD. Thus, the current study determined the effects of cognitive load on WM, using a visuo-spatial WM capacity task in children with and without ASD with functional magnetic resonance imaging (fMRI).

Methods

We used fMRI and a 1-back colour matching task (CMT) task with four levels of difficulty to compare the cortical activation patterns associated with WM in children (7–13 years old) with high functioning autism (N = 19) and matched controls (N = 17) across cognitive load.

Results

Performance on CMT was comparable between groups, with the exception of one difficulty level. Using linear trend analyses, the control group showed increasing activation as a function of difficulty level in frontal and parietal lobes, particularly between the highest difficulty levels, and decreasing activation as a function of difficulty level in the posterior cingulate and medial frontal gyri. In contrast, children with ASD showed increasing activation only in posterior brain regions and decreasing activation in the posterior cingulate and medial frontal gyri, as a function of difficulty level. Significant differences were found in the precuneus, dorsolateral prefrontal cortex and medial premotor cortex, where control children showed greater positive linear relations between cortical activity and task difficulty level, particularly at the highest difficulty levels, but children with ASD did not show these trends.

Conclusions

Children with ASD showed differences in activation in the frontal and parietal lobes—both critical substrates for visuo-spatial WM. Our data suggest that children with ASD rely mainly on posterior brain regions associated with visual and lower level processing, whereas controls showed activity in frontal lobes related to the classic WM network. Findings will help guide future work by localizing areas of vulnerability to developmental disturbances.     

White matter integrity and behavioral activation in healthy subjects

Individual differences in behavioral inhibition and behavioral activation may place certain people at greater risk for neuropsychiatric disorders and engagement in risky behaviors. Therefore, studying the neural correlates of behavioral inhibition and activation may help us understand neural mechanisms underlying risk behaviors in both clinical and non-clinical populations. To investigate, we assessed the relationships between white matter integrity and measures of behavioral inhibition and behavioral activation in 51 healthy participants using diffusion tensor imaging (DTI) and the Behavioral Inhibition System/Behavioral Activation System (BIS/BAS) scale. Scores on the Fun-Seeking subscale of the BAS positively correlated with DTI fractional anisotropy in the left corona radiata and adjacent superior longitudinal fasciculus, and with mean diffusivity in the left inferior longitudinal fasciculus and inferior fronto-occipital fasciculus after controlling for age, gender, and education. These findings suggest that the integrity of white matter connecting extensive brain regions implicated in self-control and the processing of rewards and emotions are associated with individual differences in the motivation for seeking and participating in fun and novel experiences.     

Executive functioning and verbal memory in young patients with unipolar depression and schizophrenia

Although neuropsychological studies have consistently reported executive deficits in schizophrenia, studies of executive functions in depression have produced equivocal results. The aim of this study was to examine the profile and the specificity of the executive impairment and its association with memory performance in young patients with unipolar depression. We compared patients with depression to normal control subjects and schizophrenics. Twenty young inpatients with unipolar depression, 14 schizophrenics and 20 age-, education- and IQ-matched control subjects were assessed with a neuropsychological battery including: (1) verbal memory task; (2) frontal tasks (WCST, Cognitive Estimate, Verbal fluency, verbal and visuo-spatial span) and a new complex sorting test (Delis test). Depressed patients and schizophrenics exhibited executive deficits. Unlike schizophrenics, depressed patients did not show memory impairment. Deficits in several 'higher-level' functions combined to produce executive impairments in patients with depression including complex integration for concept formation, spontaneous cognitive flexibility and initiation ability. Impaired functions in schizophrenia and in depressed patients were similar but were differently related to clinical variables. The pattern of memory failure in our schizophrenics is believed to reflect retrieval and encoding deficits. Our findings highlight the heterogeneity of skills grouped under the term 'executive functions' that are vulnerable in depression or schizophrenia.     

White matter in infancy is prospectively associated with language outcomes in kindergarten

Language acquisition is of central importance to child development. Although this developmental trajectory is shaped by experience postnatally, the neural basis for language emerges prenatally. Thus, a fundamental question remains: do structural foundations for language in infancy predict long-term language abilities? Longitudinal investigation of 40 children from infancy to kindergarten reveals that white matter in infancy is prospectively associated with subsequent language abilities, specifically between: (i) left arcuate fasciculus and phonological awareness and vocabulary knowledge, (ii) left corticospinal tract and phonological awareness, and bilateral corticospinal tract with phonological memory; controlling for age, cognitive, and environmental factors. Findings link white matter in infancy with school-age language abilities, suggesting that white matter organization in infancy sets a foundation for long-term language development.     

Lifelong bilingualism contributes to cognitive reserve against white matter integrity declines in aging

Recent evidence suggests that lifelong bilingualism may contribute to cognitive reserve (CR) in normal aging. However, there is currently no neuroimaging evidence to suggest that lifelong bilinguals can retain normal cognitive functioning in the face of age-related neurodegeneration. Here we explored this issue by comparing white matter (WM) integrity and gray matter (GM) volumetric patterns of older adult lifelong bilinguals (N=20) and monolinguals (N=20). The groups were matched on a range of relevant cognitive test scores and on the established CR variables of education, socioeconomic status and intelligence. Participants underwent high-resolution structural imaging for assessment of GM volume and diffusion tensor imaging (DTI) for assessment of WM integrity. Results indicated significantly lower microstructural integrity in the bilingual group in several WM tracts. In particular, compared to their monolingual peers, the bilingual group showed lower fractional anisotropy and/or higher radial diffusivity in the inferior longitudinal fasciculus/inferior fronto-occipital fasciculus bilaterally, the fornix, and multiple portions of the corpus callosum. There were no group differences in GM volume. Our results suggest that lifelong bilingualism contributes to CR against WM integrity declines in aging.     

Cognitive Outcomes in Patients with Frontal Lobe Epilepsy

Summary:  A typical "cognitive profile" or defining behavioral syndrome for patients with frontal lobe epilepsy (FLE) has not been described. While there have been numerous reports of impaired "executive functions" in this population, the nature and severity of these deficits is highly variable, ranging from impaired attention to difficulty with the more complex behaviors involved in planning, selecting goals, anticipating outcomes, and initiating action. These findings have been more difficult to demonstrate in children, in part due to the later appearance of these abilities in normal development. When a clear focal seizure onset is identified, or in cases of a structural lesion, cognitive impairment may be specific to the side, size, and localization of the abnormal cortex. Children who have undergone surgical resection of the dominant frontal lobe frequently show declines in verbal fluency, and sometimes verbal IQ, visual confrontation naming, and conceptual reasoning. Adult surgical cases have shown the most specific frontal lobe findings, including reduced word fluency with relatively small lesions of the dominant dorsolateral frontal cortex, the analogous finding of impaired nonverbal fluency with nondominant frontal lesions, and other executive deficits following large resections of prefrontal cortex bilaterally. These reports support the likelihood that it may not be possible to identify a specific cognitive syndrome associated with FLE in the absence of a structural lesion.