Interactive effects of APOE and CHRNA4 on attention and white matter volume in healthy middle-aged and older adults

In the present study, we investigated age-related changes in interactions between efficiency of neuronal repair mechanisms and efficiency of cholinergic neurotransmission in the context of attentional orienting. In addition, we explored white matter volume changes as possible neuronal underpinnings. A sample of 230 healthy middle-aged (53–64 years) and older (65–75 years) adults was genotyped for polymorphisms of APOE and CHRNA4, a nicotinic receptor subunit gene. Participants were administered a visuospatial attention task involving letter discrimination with location cues of varying validity. Genotype effects on white matter volume were also investigated in a subset of participants who received MRI scans. APOE interacted with CHRNA4, such that APOE-ε4 carriers who were also CHRNA4 TT homozygotes showed disproportionately slowed reaction time (RT) following invalid location cues. The interaction was stronger in the middle-aged participants than in the older participants. There was also a trend for individuals with combined APOE-ε4/CHRNA4 TT genotypes to show both lower white matter volume and slower overall RT on the attention task. The interaction of a neurotransmission gene (CHRNA4) and a susceptibility gene (APOE) suggests that the efficiency of neuronal repair mechanisms may modulate the cholinergic system to influence attentional function.     

Dichotic listening,executive functions and grey matter cortical volume in patients with schizophrenia and healthy controls

Schizophrenia is characterized by cognitive impairment, especially in relation to executive functions. Brain structural abnormalities are also often seen in schizophrenia although little is known of the relationship between cognitive impairment and structural brain changes. Our aim was therefore to investigate this relationship further using MRI and a dichotic listening (DL) task with simple speech sounds and with instructions to focus attention and report only from the left or right ear stimulus. When instructed to focus attention on the left ear syllable a cognitive conflict is induced requiring the allocation of executive resources to be resolved. Grey matter (GM) volume was measured with MRI from four volumes of interests (VOIs), left and right frontal and temporal cortex, respectively, and correlated with DL performance. The results showed significant differences between the groups in their ability to focus attention on and report the left ear stimulus, which was accompanied by reduced GM volume in the left frontal and right temporal lobe VOIs. There was also a significant positive correlation between left frontal GM volume and performance on the DL task, for the groups combined. The results did not support a conclusion that an impairment in cognitive function in schizophrenia was driven by an corresponding impairment in brain structure, since there were no significant correlations when the groups were analyzed separately. It is however concluded that patients with schizophrenia are impaired in executive functions and that they also show reduced GM volumes in left frontal and right temporal lobe areas, compared to healthy controls.     

White matter development during adolescence as shown by diffusion MRI

Previous volumetric developmental MRI studies of the brain have shown white matter development continuing through adolescence and into adulthood. This review presents current findings regarding white matter development and organization from diffusion MRI studies. The general trend during adolescence (age 12–18 years) is towards increasing fractional anisotropy (FA) with age and decreasing mean diffusivity (MD) with age, findings primarily due to decreasing radial diffusivity with age. However, results of studies vary as to the regional specificity of such age-related changes, likely due in part to methodological issues. Another general trend is for FA to positively correlate and MD to negatively correlate with cognitive function. This trend is however region-specific, task-specific, and population-specific; some studies have in fact found negative correlations of FA and positive correlations of MD in specific regions with specific measures of cognitive performance. There are also published reports of sexual dimorphism in white matter development, indicating differing developmental trajectories between males and females as well as differing relationships developmentally between white matter architecture and cognitive function. There is a need for more research to further elucidate the development of white matter and its relation to cognitive function during this critical developmental period.     

Sex differences in parietal lobe morphology: relationship to mental rotation performance

Structural magnetic resonance imaging (MRI) studies of the human brain have reported evidence for sexual dimorphism. In addition to sex differences in overall cerebral volume, differences in the proportion of gray matter (GM) to white matter (WM) volume have been observed, particularly in the parietal lobe. To our knowledge there have been no studies examining the relationship between the sex differences in parietal lobe structure and function. The parietal lobe is thought to be involved in spatial ability, and particularly involved in mental rotation. The purpose of this study is to examine whether sex differences in parietal lobe structure are present, and if present to relate these differences to performance on the mental rotations test (MRT). We found that women had proportionately greater gray matter volume in the parietal lobe compared to men, and this morphologic difference was disadvantageous for women in terms of performance on the MRT. In contrast, we found that men compared to women had proportionately greater parietal lobe surface area, and this morphologic difference was associated with a performance advantage for men on mental rotation. These findings support the possibility that the sexual dimorphism in the structure of the parietal lobe is a neurobiological substrate for the sex difference in performance on the mental rotations test.     

Processing speed in normal aging: Effects of white matter hyperintensities and hippocampal volume loss

Changes in cognitive functioning are said to be part of normal aging. Quantitative MRI has made it possible to measure structural brain changes during aging which may underlie these decrements which include slowed information processing and memory loss. Much has been written on white matter hyperintensities (WMH), which are associated with cognitive deficits on tasks requiring processing speed and executive functioning, and hippocampal volume loss, which is associated with memory decline. Here we examine volumetric MRI measures of WMH and hippocampal volume loss together in relation to neuropsychological tests considered to be measures of executive functioning and processing speed in 81 non-demented elderly individuals, aged 75–90. Correlational analysis showed that when controlling for age, both greater WMH volume and smaller hippocampal volume were correlated with slower performances on most tests with the exception of a battery of continuous performance tests in which only WMH was correlated with slower reaction time (RT). We then performed a series of hierarchical multiple regression analyses to examine the independent contributions of greater WMH volume and reduced hippocampal volume to executive functioning and processing speed. The results showed that for the four measures requiring executive functioning and speed of processing, WMH volume and hippocampal volume combined predicted between 21.4% and 37% of the explained variance. These results suggest that WM integrity and hippocampal volume influence cognitive decline independently on tasks involving processing speed and executive function independent of age.     

Brain abnormalities observed in childhood-onset schizophrenia: a review of the structural magnetic resonance imaging literature

Childhood-onset schizophrenia (COS) is a rare, severe form of schizophrenia in which there are structural brain abnormalities that may be related to the psychotic symptomatology and neurocognitive deficits found in these patients. While there are numerous structural imaging studies of the adult-onset variant of schizophrenia (with many conflicting findings), relatively few brain imaging studies of COS have been conducted. This paper summarizes the extant literature of magnetic resonance imaging (MRI) studies of structural brain abnormalities in COS, and compares findings to similar studies of adult-onset patients. Volumetric MRI studies of COS patients have consistently shown evidence for increased ventricular volume, reduced cerebral gray matter, and increased caudate volume, consistent with findings from adult-onset studies. Other volumetric brain abnormalities are observed in COS patients, such as reduced total brain volume, but not consistently across all studies. Voxel-based morphometric analyses have revealed abnormalities in the shape and spatial location of structures in COS such as the corpus callosum, caudate, and thalamus that could not be observed in the more traditional volumetric assessments. Similar findings also are observed in adult-onset patients. Progressive degenerative changes, such as ventricular enlargement, appear to occur in COS only until young adulthood where there is an apparent asymptote with no further degenerative changes. This is consistent with the lack of progressive changes noted in most longitudinal studies of adult-onset schizophrenia.     

Structural brain abnormalities in patients with Parkinson’s disease with visual hallucinations: A comparative voxel-based analysis

The objective is to evaluate clinical characteristics and cerebral alterations in Parkinson’s disease (PD) patients with diurnal visual hallucinations (VHs). Assessment was performed using magnetic resonance image (MRI) and voxel-based morphometry (VBM). Thirty-nine patients with PD (53.8%) and ten controls were studied. Voxel based morphology analysis was performed. Eleven patients presented diurnal VHs and among these, six had cognitive dysfunction. Patients with VHs performed worse in the mentation-related UPDRS I (p = 0.005) and motor-related UPDRS III (p = 0.02). Patients with VHs showed significant clusters of reduced grey matter volume compared to controls in the left opercula frontal gyrus and left superior frontal gyrus. PD without hallucinations demonstrated reduced grey matter volume in the left superior frontal gyrus compared to controls. Comparisons between patients with VHs regarding the presence of cognitive dysfunction showed that cases with cognitive dysfunction as compared to those without cognitive dysfunction showed significant clusters of reduced grey matter volume in the left opercular frontal gyrus. Cases without cognitive dysfunction had reduced grey matter substance in the left insula and left trigonal frontal gyrus. Judging from our findings, an abnormal frontal cortex, particularly left sided insula, frontal opercular, trigonal frontal gyrus and orbital frontal would make PD patients vulnerable to hallucinations. Compromise of the left operculum distinguished cases with VHs and cognitive dysfunction. Our findings reinforce the theoretical concept of a top-down visual processing in the genesis of VHs in PD.     

Correlation between gray/white matter volume and cognition in healthy elderly people

This study applied volumetric analysis and voxel-based morphometry (VBM) of brain magnetic resonance (MR) images to assess whether correlations exist between global and regional gray/white matter volume and the cognitive functions of semantic memory and short-term memory, which are relatively well preserved with aging, using MR image data from 109 community-dwelling healthy elderly individuals. We used the Information and Digit Span subtests of the Wechsler Adult Intelligent Scale-Revised as measures of semantic memory and short-term memory, respectively. We found significant positive correlations between the gray matter ratio, the percentage of gray matter volume in the intracranial volume, and performance on the Digit Span subtest, and between the regional gray matter volumes of the bilateral anterior temporal lobes and performance on the Information subtest. No significant correlations between performance on the cognitive tests and white matter volume were found. Our results suggest that individual variability in specific cognitive functions that are relatively well preserved with aging is accounted for by the variability of gray matter volume in healthy elderly subjects.     

Effect of socioeconomic status (SES) disparity on neural development in female African‐American infants at age 1 month

There is increasing interest in both the cumulative and long‐term impact of early life adversity on brain structure and function, especially as the brain is both highly vulnerable and highly adaptive during childhood. Relationships between SES and neural development have been shown in children older than age 2 years. Less is known regarding the impact of SES on neural development in children before age 2. This paper examines the effect of SES, indexed by income‐to‐needs (ITN) and maternal education, on cortical gray, deep gray, and white matter volumes in term, healthy, appropriate for gestational age, African‐American, female infants. At 5 weeks postnatal age, unsedated infants underwent MRI (3.0T Siemens Verio scanner, 32‐channel head coil). Images were segmented based on a locally constructed template. Utilizing hierarchical linear regression, SES effects on MRI volumes were examined. In this cohort of healthy African‐American female infants of varying SES, lower SES was associated with smaller cortical gray and deep gray matter volumes. These SES effects on neural outcome at such a young age build on similar studies of older children, suggesting that the biological embedding of adversity may occur very early in development.     

Larger brain and white matter volumes in children with developmental language disorder

Developmental language disorder (DLD) is predominantly a language disorder, but children with DLD also manifest non-language impairments, and neuroanatomical abnormalities have been found in multiple areas of the brain, not all language-associated. We therefore performed a whole brain general segmentation analysis of all major brain regions on MRI scans of 24 DLD subjects (16M, 8F) and 30 controls (15M, 15F), ages 5.7 to 11.3 years. Children with DLD showed increased total brain volume, driven predominantly by a substantial increase in the volume of cerebral white matter. Cerebral cortex and caudate were relatively but not absolutely smaller in DLD. These findings are discussed in relation to issues of specificity vs. generality as they arise in debates about (1) modular vs. general processing deficits and connectionist modeling in DLD, (2) language-specific vs. pervasive, non-specific deficits in DLD and (3) specificity of the disorder vs. overlap with other disorders, notably autism.     

Are nonlinguistic functions in "Broca's area" prerequisites for language acquisition? FMRI findings from an ontogenetic viewpoint

There is incomplete consensus on the anatomical demarcation of Broca's area in the left inferior frontal gyrus and its functional characterization remains a matter of debate. Exclusive syntactic specialization has been proposed, but is overall inconsistent with the neuroimaging literature. We examined three functional MRI (fMRI) datasets on lexicosemantic decision, tone discrimination, and visuomotor coordination for potential overlap of activation. A single site of convergent activation across all three paradigms was found in the left inferior frontal lobe (area 44/45). This result is discussed in the context of animal and human studies showing inferior frontal participation in visuomotor and audiomotor functions as well as working memory. We propose that Broca's area involvement in lexical semantics and syntax emerges from these nonlinguistic functions, which are prerequisites for language acquisition.     

What Does Diffusion Tensor Imaging Reveal About the Brain and Cognition in Fetal Alcohol Spectrum Disorders?

Over the past 5 years, Diffusion Tensor Imaging (DTI) has begun to provide new evidence about the effects of prenatal alcohol exposure on white matter development. DTI, which examines microstructural tissue integrity, is sensitive to more subtle white matter abnormalities than traditional volumetric MRI methods. Thus far, the available DTI data suggest that white matter microstructural abnormalities fall on a continuum of severity in Fetal Alcohol Spectrum Disorder (FASD). Abnormalities are prominent in the corpus callosum, but also evident in major anterior-posterior fiber bundles, corticospinal tracts, and cerebellum. These subtle abnormalities are correlated with neurocognitive deficits, especially in processing speed, non-verbal ability, and executive functioning. Future studies using larger samples, increasingly sophisticated DTI methods, and additional functional MRI connectivity measures will better characterize the full range of abnormalities in FASD. Ultimately, these measures may serve as indices of change in future longitudinal studies and in studies of interventions for FASD.     

Air pollution, cognitive deficits and brain abnormalities: a pilot study with children and dogs

Exposure to air pollution is associated with neuroinflammation in healthy children and dogs in Mexico City. Comparative studies were carried out in healthy children and young dogs similarly exposed to ambient pollution in Mexico City. Children from Mexico City (n: 55) and a low polluted city (n:18) underwent psychometric testing and brain magnetic resonance imaging MRI. Seven healthy young dogs with similar exposure to Mexico City air pollution had brain MRI, measurement of mRNA abundance of two inflammatory genes cyclooxygenase-2, and interleukin 1 beta in target brain areas, and histopathological evaluation of brain tissue. Children with no known risk factors for neurological or cognitive disorders residing in a polluted urban environment exhibited significant deficits in a combination of fluid and crystallized cognition tasks. Fifty-six percent of Mexico City children tested showed prefrontal white matter hyperintense lesions and similar lesions were observed in dogs (57%). Exposed dogs had frontal lesions with vascular subcortical pathology associated with neuroinflammation, enlarged Virchow-Robin spaces, gliosis, and ultrafine particulate matter deposition. Based on the MRI findings, the prefrontal cortex was a target anatomical region in Mexico City children and its damage could have contributed to their cognitive dysfunction. The present work presents a groundbreaking, interdisciplinary methodology for addressing relationships between environmental pollution, structural brain alterations by MRI, and cognitive deficits/delays in healthy children.     

老年人整体运动敏感性降低的脑灰质体积变化基础

本研究使用多体素模式分析方法和随机点阵范式,首次探索了老年人整体运动敏感性（GMS）下降和其脑灰质体积下降间的关系。结果发现,老年人GMS显著低于年轻人,老年人V5/MT、V3和额顶等脑区灰质体积显著小于年轻人;V5/MT和V3区的灰质体积信号可以有效预测个体的GMS。结果提示,V5/MT区和V3区,特别是V3区的灰质体积下降可能是老年人GMS下降的主要原因;而基于“去分化假设”,全脑范围内其余脑区的灰质体积下降可能也在一定程度上与老年人GMS下降有关。     

Regional cortical volume and cognitive functioning following traumatic brain injury

There has been limited examination of the effect of brain pathology on subsequent function. The current study examined the relationships between regional variation in grey matter volume, age and cognitive impairment using a semi-automated image analysis tool. This study included 69 individuals with mild-to-severe TBI, 41 of whom also completed neuropsychological tests of attention, working memory, processing speed, memory and executive functions. A widespread reduction in grey matter volume was associated with increasing age. Regional volumes that were affected also related to the severity of injury, whereby the most severe TBI participants displayed the most significant pathology. Poorer retention of newly learned material was associated with reduced cortical volume in frontal, parietal, and occipital brain regions. In addition, poorer working memory and executive control performance was found for individuals with lower cortical volume in temporal, parietal, and occipital regions. These findings are largely in line with previous literature, which suggests that frontal, temporal, and parietal regions are integral for the encoding of memories into long-term storage, memory retrieval, and working memory. The present study suggests that automated image analysis methods may be used to explore the relationships between regional variation in grey matter volume and cognitive function following TBI.     

The Importance of the Default Mode Network in Creativity—A Structural MRI Study

Anecdotal reports as well as behavioral studies have suggested that creative performance benefits from unconscious processes. So far, however, little is known about how creative ideas arise from the brain. In the current study, we aimed to investigate the neural correlates of creativity by means of structural MRI research. Given that unconscious and less controlled processes are important in creative thinking, structural brain research may find a positive correlation between well‐established creativity measures and cortical thickness in brain structures of the default mode network (i.e., the counterpart of the cognitive control network). Individuals performed the Alternative Uses task by which an individual's cognitive flexibility and the average uniqueness and average creativity of a participant's ideas were assessed. We computed optimized voxel‐based‐morphometry (VBM) to explore the correlation between inter‐individual differences in creativity and inter‐individual differences in gray matter volume. For all creativity measures, a positive correlation was found between creative performance and gray matter volume of the default mode network. These findings support the idea that the default mode network is important in creativity, and provide neurostructural support for the idea that unconscious forms of information processing are important in creativity. Theoretical and practical implications are discussed.     

The hippocampus and delayed recall: bigger is not necessarily better?

Healthy young female participants were tested on a measure of delayed verbal recall and then received volumetric Magnetic Resonance Imaging (MRI) scans. The analysis of the MRI scans focused on the volume of the hippocampus. Left hippocampal volume was negatively associated with the level of delayed verbal recall performance. This relationship was confirmed in further testing. This finding is consistent with a previous report of a similar relationship in healthy elderly individuals, but not in patients with Alzheimer's disease, in whom the opposite relationship was observed. An explanation of these findings in terms of impaired neural pruning of the hippocampus is advanced, whereby insufficient pruning of the hippocampus during childhood and adolescence (following adequate growth) may lead to reduced mnemonic efficiency.     

MRI-Assessed Volume of Cerebellum Correlates with Associative Learning

Richard F. Thompson's cerebellar model of classical eyeblink conditioning highlights Purkinje cells in cerebellar cortex and principal cells in the deep cerebellar nucleus as the integrating cells for acquisition of conditioned responses (CRs). CR acquisition is significantly slower in rabbits with lesions to cerebellar cortex and in Purkinje cell-deficient mice that lose all cerebellar cortical Purkinje cells. Purkinje cells are the largest neurons in the cerebellum and contribute significantly to cerebellar volume. Magnetic resonance imaging (MRI) was used to assess cerebellar volume in humans. Cerebellar volume was related to eyeblink conditioning (400-ms delay procedure) in 8 adults (21-35 years) and compared to 8 older adults (77-95 years) tested previously (Woodruff-Pak, Goldenberg, Downey-Lamb, Boyko, & Lemieux, 2000). In the young adult sample, there was a high correlation between percentage of CRs in a session and cerebellar volume (corrected for total intracranial volume [TIV], r =.58, p =.066). There were statistically significant age differences in cerebellar volume, t(14) = 8.96, p <.001, and percentage of CRs, t(14) = 3.85, p <.002, but no age difference in TIV. Combining the young and older adult sample, the correlation between percentage of CRs and cerebellar volume (corrected for TIV) was.832 (p <.001). Cerebellar volume showed age-related deficits likely due to Purkinje cell loss. Individual differences in classical eyeblink conditioning are associated with differences in cerebellar volume, supporting Thompson's model of a cerebellar cortical role in facilitating this form of associative learning.     

Association of television violence exposure with executive functioning and white matter volume in young adult males

Prior research has indicated that self-reported violent media exposure is associated with poorer performance on some neuropsychological tests in adolescents. This study aimed to examine the relationship of executive functioning to violent television viewing in healthy young adult males and examine how brain structure is associated with media exposure measures. Sixty-five healthy adult males (ages 18–29) with minimal video game experience estimated their television viewing habits over the past year and, during the subsequent week, recorded television viewing time and characteristics in a daily media diary. Participants then completed a battery of neuropsychological laboratory tests quantifying executive functions and underwent a magnetic resonance imaging (MRI) scan. Aggregate measures of executive functioning were not associated with measures of overall television viewing (any content type) during the past week or year. However, the amount of television viewing of violent content only, as indicated by both past-year and daily diary measures, was associated with poorer scores on an aggregate score of inhibition, interference control and attention, with no relationship to a composite working memory score. In addition, violent television exposure, as measured with daily media diaries, was associated with reduced frontoparietal white matter volume. Future longitudinal work is necessary to resolve whether individuals with poor executive function and slower white matter growth are more drawn to violent programming, or if extensive media violence exposure modifies cognitive control mechanisms mediated primarily via prefrontal cortex. Impaired inhibitory mechanisms may be related to reported increases in aggression with higher media violence exposure.     

Variability in perisylvian brain anatomy in healthy adults

Gray matter volumes of Heschl's gyrus (HG), planum temporale (PT), pars triangularis (PTR), and pars opercularis were measured on MRI in 48 healthy right-handers. There was the expected leftward PT asymmetry in 70.8%, and leftward PTR asymmetry in 64.6% of the sample. When asymmetry patterns within individuals were examined, there was not one typical pattern, rather several typical configurations were found. In addition, some combinations of asymmetry did not exist in our sample suggesting that some perisylvian anatomical configurations may provide a more suitable neural substrate for the development of language than others. There were also sex differences in HG. Men had rightward asymmetry and women demonstrated leftward asymmetry, due to women having smaller right HG, compared to men.