Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using the noninvasive transcranial ultrasonic Doppler method, flow dynamics of the middle cerebral arteries were investigated in relation to auditory stimulations in 12 children with autistic behavior compared with 12 normal controls and 10 mentally retarded children. In normal children, auditory stimulation evoked lateralized modifications: blood flow increased and resistance index decreased on the left side; such modifications were not recorded on the right side. This pattern should indicate vasodilatation mechanisms induced by changes in the metabolism of the brain areas supplied by the left middle cerebral arteries (MCA). Although less asymmetrical, this pattern was also found in the mentally retarded children. Autistic children significantly differed from these two groups. They displayed a symmetric pattern of responses with a blood flow decrease and resistance-index increase on both sides; this could suggest abnormal metabolic mechanisms induced by auditory stimulation in autistic children and could be related to the previous hypothesis of impairment in the development of cerebral lateralization in autism. These preliminary results show that transcranial Doppler ultrasonography may be a valuable and practicable tool for the noninvasive study of evoked blood flow responses in psychopathology.
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PMID:Blood flow response to auditory stimulations in normal, mentally retarded, and autistic children: a preliminary transcranial Doppler ultrasonographic study of the middle cerebral arteries. 145 24

We report a whole-brain MRI morphometric survey of asymmetry in children with high-functioning autism and with developmental language disorder (DLD). Subjects included 46 boys of normal intelligence aged 5.7-11.3 years (16 autistic, 15 DLD, 15 controls). Imaging analysis included grey-white segmentation and cortical parcellation. Asymmetry was assessed at a series of nested levels. We found that asymmetries were masked with larger units of analysis but progressively more apparent with smaller units, and that within the cerebral cortex the differences were greatest in higher-order association cortex. The larger units of analysis, including the cerebral hemispheres, the major grey and white matter structures and the cortical lobes, showed no asymmetries in autism or DLD and few asymmetries in controls. However, at the level of cortical parcellation units, autism and DLD showed more asymmetry than controls. They had a greater aggregate volume of significantly asymmetrical cortical parcellation units (leftward plus rightward), as well as a substantially larger aggregate volume of right-asymmetrical cortex in DLD and autism than in controls; this rightward bias was more pronounced in autism than in DLD. DLD, but not autism, showed a small but significant loss of leftward asymmetry compared with controls. Right : left ratios were reversed, autism and DLD having twice as much right- as left-asymmetrical cortex, while the reverse was found in the control sample. Asymmetry differences between groups were most significant in the higher-order association areas. Autism and DLD were much more similar to each other in patterns of asymmetry throughout the cerebral cortex than either was to controls; this similarity suggests systematic and related alterations rather than random neural systems alterations. We review these findings in relation to previously reported volumetric features in these two samples of brains, including increased total brain and white matter volumes and lack of increase in the size of the corpus callosum. Larger brain volume has previously been associated with increased lateralization. The sizeable right-asymmetry increase reported here may be a consequence of early abnormal brain growth trajectories in these disorders, while higher-order association areas may be most vulnerable to connectivity abnormalities associated with white matter increases.
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PMID:Brain asymmetries in autism and developmental language disorder: a nested whole-brain analysis. 1556 15

Brain asymmetry is understood as an anatomical, functional or neurochemical difference between the two hemispheres. It is not a static but rather a dynamic phenomenon in which both environmental and endogenous factors act as modulators. Aging modifies brain asymmetry, and an imbalance in specific asymmetries characterizes some brain disorders such as schizophrenia, depression, infantile autism or Alzheimer's disease. However, it is not clear whether these changes are a cause or a consequence of these disorders. Although this phenomenon has been extensively studied, its functional significance is not yet clear, and the neurochemical basis underlying anatomical or functional asymmetries in the brain is still poorly understood. In recent decades intensive research on the behaviour of neuropeptides has revealed asymmetries in their distribution in the brain, and there is evidence that the lateralized patterns of distribution are involved in the regulatory control of some neuropeptidase activities. Therefore, if these enzymatic activities are distributed asymmetrically, their endogenous substrates would presumably be affected in an asymmetrical way, as would the functions they are involved in. Here we review the most significant literature regarding human and animal brain asymmetry involving neuropeptides such as corticotropin-releasing hormone, cholecystokinin, luteinizing hormone-releasing hormone, thyrotropin-releasing hormone and angiotensin II, as well as their neuropeptidases.
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PMID:Neuropeptides, neuropeptidases and brain asymmetry. 1558 19

Evidence is presented that RHD, RHCE, and other RH genes, may be interesting candidates to consider when searching for the genetic basis of hair whorl rotation (i.e., clockwise or counterclockwise), handedness (i.e., right handed, left handed or ambidextrous), speech laterality (i.e., right brained or left brained), speech dyslexia (e.g., stuttering), sexual orientation (i.e., heterosexual, homosexual, bisexual, or transsexual), schizophrenia, bipolar disorder, and autism spectrum disorder. Such evidence involves the need for a genetic model that includes maternal immunization to explain some of the empirical results reported in the literature. The complex polymorphisms present among the maternally immunizing RH genes can then be used to explain other empirical results. Easily tested hypotheses are suggested, based upon genotypic (but not phenotypic) frequencies of the RH genes. In particular, homozygous dominant individuals are expected to be less common or lacking entirely among the alternative phenotypes. If it is proven that RH genes are involved in brain architecture, it will have a profound effect upon our understanding of the development and organization of the asymmetrical vertebrate brain and may eventually lead to a better understanding of the developmental processes which occur to produce the various alternative phenotypes discussed here. In addition, if RH genes are shown to be involved in the production of these phenotypes, then the evolutionary studies can be performed to demonstrate the beneficial effect of the recessive alleles of RHD and RHCE, and why human evolution appears to be selecting for the recessive alleles even though an increase in the frequency of such alleles may imply lower average fecundity among some individuals possessing them.
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PMID:The genetic basis of hair whorl, handedness, and other phenotypes. 1633 93

Bipedal locomotion and fine motility of hand and larynx of humans introduced musculoskeletal adaptations, new pyramidal, corticostriatal, corticobulbar, nigrostriatal, and cerebellar pathways and expansions of prefrontal, cingular, parieto-temporal and occipital cortices with derived new brain capabilities. All selectively degenerate in aged homo sapiens following 16 syndromic presentations: (1) Parkinsonism: nigrostriatal control for fast automatic movements of hand, larynx, bipedal posture and gait ("simian gait and hand"). (2) Frontal (highest level) gait disorders (lower body parkinsonism, gait apraxia, retropulsion): prefrontostriatal executive control of bipedal locomotion. (3) ataxia: new synergistic coordination of bipedal gait and fine motility. (4) Dyskinesias (chorea, dystonia, tremor...): intrusions of simian basal ganglia motor subroutines. (5) motoneuron diseases: new proximo-distal and bulbar motoneurones, preserving older ones (oculomotor, abdominal...). (6) Archaic reflexes: prefrontal disinhibition of old mother/tree-climbing-oriented reflexes (sucking, grasping, Babinski/triple retraction, gegenhalten), group alarms (laughter, crying, yawning, grunting...) or grooming (tremor=scratching). (7) Dysautonomia: contextual regulation (orthostatism...). (8) REM sleep disorders of new cortical functions. (9) Corticobasal syndrome: melokinetic control of hand prehension-manipulation and language (retrocession to simian patterns). (10) Frontal/temporal lobe degeneration: medial-orbitofrontal behavioural variant: self monitoring of internal needs and social context: apathy, loss of personal hygiene, stereotypia, disinhibition, loss of concern for consequences of acts, social rules, danger and empathy; dorsolateral executive variant: inadequacy to the context of action (goal, environmental changes...); progressive non-fluent aphasia: executive and praxic processing of speech; temporal variant: abstract concepts for speech, gestures and vision (semantic dementia, progressive nonfluent aphasia) (11) Temporomesial-limbic-paralimbic-associative cortical dementias (Alzheimer's disease, Lewy body, progressive amnesia): processing of explicit cognition: amnesic syndrome, processing of hand, larynx and eye: disorientation, ideomotor apraxia, agnosia, visuospatial processing, transcortical aphasia. (12) Focal posterior atrophy (Benson, progressive apraxia): visuomotor processing of what and where. (13) Macular degeneration: retinal "spot" for explicit symbols. (14) "Psychiatric syndromes": metacognition, self monitoring and regulation of hierarchical processing of metacognition: hallucinations, delusions, magic and mystic logic, delusions, confabulations; drive: impulsivity, obsessive-compulsive disorders, mental automatisms; social interactions: theory of mind, autism, Asperger. (15) Mood disorders: control on emotions: anxio-depressive and bipolar disorders, moria, emotional lability. (16) Musculoskeletal: inclusion body myositis: muscles for bipedal gait and fine motility. Paget's disease: bones for bipedal gait and cranium. Understanding of the genetic mechanisms underlying the evolution of these recent human brain regions and paleoneurology my be the key to the focal, asymmetrical or systemic character of neurodegeneration, the pathologic heterogeneity/overlap of syndromic presentations associating gait, hand, language, cognition, mood and behaviour disorders.
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PMID:Paleoneurology: neurodegenerative diseases are age-related diseases of specific brain regions recently developed by Homo sapiens. 1870 90

This study examines the link between children's repetitive, ritualistic, behavior and cortical brain activity. Twelve typically developing children between the ages of 6 and 12 years were administered two visual P300, oddball tasks with a 32-electrode electroencephalogram (EEG) system. One of the oddball tasks was specifically designed to reflect sensitivity to asymmetry, a phenomenon common in children and in a variety of disorders involving compulsive behavior. Parents completed the Childhood Routines Inventory. Children's repetitive, compulsive-like behaviors were strongly associated with faster processing of an asymmetrical target stimulus, even when accounting for their P300 latencies on a control task. The research punctuates the continuity between observed brain-behavior links in clinical disorders such as OCD and autism spectrum disorders, and normative variants of repetitive behavior.
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PMID:Cortical activity and children's rituals, habits and other repetitive behavior: a visual P300 study. 2165 17

Lateralization of brain connectivity may be essential for normal brain function and may be sexually dimorphic. Here, we study the laterality patterns of short-range (implicated in functional specialization) and long-range (implicated in functional integration) connectivity and the gender effects on these laterality patterns. Parallel computing was used to quantify short- and long-range functional connectivity densities in 913 healthy subjects. Short-range connectivity was rightward lateralized and most asymmetrical in areas around the lateral sulcus, whereas long-range connectivity was rightward lateralized in lateral sulcus and leftward lateralizated in inferior prefrontal cortex and angular gyrus. The posterior inferior occipital cortex was leftward lateralized (short- and long-range connectivity). Males had greater rightward lateralization of brain connectivity in superior temporal (short- and long-range), inferior frontal, and inferior occipital cortices (short-range), whereas females had greater leftward lateralization of long-range connectivity in the inferior frontal cortex. The greater lateralization of the male's brain (rightward and predominantly short-range) may underlie their greater vulnerability to disorders with disrupted brain asymmetries (schizophrenia, autism).
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PMID:Laterality patterns of brain functional connectivity: gender effects. 2187 83

This study examines the links between human perceptions, cognitive biases and neural processing of symmetrical stimuli. While preferences for symmetry have largely been examined in the context of disorders such as obsessive-compulsive disorder and autism spectrum disorders, we examine various these phenomena in non-clinical subjects and suggest that such preferences are distributed throughout the typical population as part of our cognitive and neural architecture. In Experiment 1, 82 young adults reported on the frequency of their obsessive-compulsive spectrum behaviors. Subjects also performed an emotional Stroop or variant of an Implicit Association Task (the OC-CIT) developed to assess cognitive biases for symmetry. Data not only reveal that subjects evidence a cognitive conflict when asked to match images of positive affect with asymmetrical stimuli, and disgust with symmetry, but also that their slowed reaction times when asked to do so were predicted by reports of OC behavior, particularly checking behavior. In Experiment 2, 26 participants were administered an oddball Event-Related Potential task specifically designed to assess sensitivity to symmetry as well as the OC-CIT. These data revealed that reaction times on the OC-CIT were strongly predicted by frontal electrode sites indicating faster processing of an asymmetrical stimulus (unparallel lines) relative to a symmetrical stimulus (parallel lines). The results point to an overall cognitive bias linking disgust with asymmetry and suggest that such cognitive biases are reflected in neural responses to symmetrical/asymmetrical stimuli.
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PMID:Human preferences for symmetry: subjective experience, cognitive conflict and cortical brain activity. 2272 4

The presence of asymmetry in the human cerebral hemispheres is detectable at both the macroscopic and microscopic scales. The horizontal expansion of cortical surface during development (within individual brains), and across evolutionary time (between species), is largely due to the proliferation and spacing of the microscopic vertical columns of cells that form the cortex. In the asymmetric planum temporale (PT), minicolumn width asymmetry is associated with surface area asymmetry. Although the human minicolumn asymmetry is not large, it is estimated to account for a surface area asymmetry of approximately 9% of the region's size. Critically, this asymmetry of minicolumns is absent in the equivalent areas of the brains of other apes. The left-hemisphere dominance for processing speech is thought to depend, partly, on a bias for higher resolution processing across widely spaced minicolumns with less overlapping dendritic fields, whereas dense minicolumn spacing in the right hemisphere is associated with more overlapping, lower resolution, holistic processing. This concept refines the simple notion that a larger brain area is associated with dominance for a function and offers an alternative explanation associated with "processing type." This account is mechanistic in the sense that it offers a mechanism whereby asymmetrical components of structure are related to specific functional biases yielding testable predictions, rather than the generalization that "bigger is better" for any given function. Face processing provides a test case - it is the opposite of language, being dominant in the right hemisphere. Consistent with the bias for holistic, configural processing of faces, the minicolumns in the right-hemisphere fusiform gyrus are thinner than in the left hemisphere, which is associated with featural processing. Again, this asymmetry is not found in chimpanzees. The difference between hemispheres may also be seen in terms of processing speed, facilitated by asymmetric myelination of white matter tracts (Anderson et al., 1999 found that axons of the left posterior superior temporal lobe were more thickly myelinated). By cross-referencing the differences between the active fields of the two hemispheres, via tracts such as the corpus callosum, the relationship of local features to global features may be encoded. The emergent hierarchy of features within features is a recursive structure that may functionally contribute to generativity - the ability to perceive and express layers of structure and their relations to each other. The inference is that recursive generativity, an essential component of language, reflects an interaction between processing biases that may be traceable in the microstructure of the cerebral cortex. Minicolumn organization in the PT and the prefrontal cortex has been found to correlate with cognitive scores in humans. Altered minicolumn organization is also observed in neuropsychiatric disorders including autism and schizophrenia. Indeed, altered interhemispheric connections correlated with minicolumn asymmetry in schizophrenia may relate to language-processing anomalies that occur in the disorder. Schizophrenia is associated with over-interpretation of word meaning at the semantic level and over-interpretation of relevance at the level of pragmatic competence, whereas autism is associated with overly literal interpretation of word meaning and under-interpretation of social relevance at the pragmatic level. Both appear to emerge from a disruption of the ability to interpret layers of meaning and their relations to each other. This may be a consequence of disequilibrium in the processing of local and global features related to disorganization of minicolumnar units of processing.
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PMID:The cortical microstructural basis of lateralized cognition: a review. 2512 82

Abnormal cortical circuits underlie some cognitive and psychiatric disorders, yet the molecular signals that generate normal cortical networks remain poorly understood. Semaphorin 7A (Sema7A) is an atypical member of the semaphorin family that is GPI-linked, expressed principally postnatally, and enriched in sensory cortex. Significantly, SEMA7A is deleted in individuals with 15q24 microdeletion syndrome, characterized by developmental delay, autism, and sensory perceptual deficits. We studied the role that Sema7A plays in establishing functional cortical circuitry in mouse somatosensory barrel cortex. We found that Sema7A is expressed in spiny stellate cells and GABAergic interneurons and that its absence disrupts barrel cytoarchitecture, reduces asymmetrical orientation of spiny stellate cell dendrites, and functionally impairs thalamocortically evoked synaptic responses, with reduced feed-forward GABAergic inhibition. These data identify Sema7A as a regulator of thalamocortical and local circuit development in layer 4 and provide a molecular handle that can be used to explore the coordinated generation of excitatory and inhibitory cortical circuits.
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PMID:Maturation of cortical circuits requires Semaphorin 7A. 2520 75


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