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Lateral and medial hypofrontality in first-episode schizophrenia: functional activity in a medication-naive state and effects of short-term atypical antipsychotic treatment.

OBJECTIVE: The dorsolateral prefrontal cortex and the anterior cingulate cortex are critical components of the brain circuitry underlying executive control. The objective of this study was to investigate control-related dorsolateral prefrontal cortex functioning and conflict-related anterior cingulate cortex functioning in a group of never medicated first-episode schizophrenia patients to determine whether both regions show dysfunction at illness onset. A second objective was to assess short-term effects of atypical antipsychotic medication on dorsolateral prefrontal cortex and anterior cingulate cortex functioning. METHOD: First-episode schizophrenia patients (N=23) and healthy comparison subjects (N=24) underwent event-related fMRI and performed a cognitive task designed to functionally dissociate the two regions. Four weeks after initiation of pharmacotherapy for patients, a subset of 11 patients and 16 comparison subjects underwent a repeat assessment. RESULTS: At baseline, patients exhibited hypoactivation in the dorsolateral prefrontal cortex and anterior cingulate cortex. After 4 weeks of antipsychotic treatment, the patients demonstrated improved functioning in the anterior cingulate cortex but not in the dorsolateral prefrontal cortex. CONCLUSIONS: These findings confirm the presence of dorsolateral prefrontal cortex dysfunction early in the course of schizophrenia and suggest that anterior cingulate cortex functioning may be altered at illness onset as well. Results also suggest that anterior cingulate cortex functioning may be especially sensitive to remedial antipsychotic treatment effects. These findings are consistent with an emerging literature documenting short-term benefits of atypical antipsychotic medication for the neural circuitry underlying cognitive deficits in schizophrenia.

Adult↗

New tests of vestibular function.

Three new, simple, clinically applicable tests of vestibular function are described. The first is a test of the response of the lateral semicircular canals to high accelerations. The test can even be done at the bedside where it can reveal severe unilateral or bilateral loss of lateral canal function. The test can also be recorded in a laboratory where it might show a less severe deficit of lateral canal function. The second is a simple, laboratory test of utricular function which depends on a subject's ability to align a bar with the subjective visual vertical. Patients with acute unilateral peripheral vestibular lesions invariably set the bar toward the side of the lesion. The third is a laboratory test of saccular function relying on a click-evoked inhibitory vestibulo-collic reflex recorded in the ipsilateral sternomastoid muscle. It can be done with equipment used for auditory evoked potentials.

Functional Laterality↗

Searching for neuronal left/right asymmetry: genomewide analysis of nematode receptor-type guanylyl cyclases.

Functional left/right asymmetry ("laterality") is a fundamental feature of many nervous systems, but only very few molecular correlates to functional laterality are known. At least two classes of chemosensory neurons in the nematode Caenorhabditis elegans are functionally lateralized. The gustatory neurons ASE left (ASEL) and ASE right (ASER) are two bilaterally symmetric neurons that sense distinct chemosensory cues and express a distinct set of four known chemoreceptors of the guanylyl cyclase (gcy) gene family. To examine the extent of lateralization of gcy gene expression patterns in the ASE neurons, we have undertaken a genomewide analysis of all gcy genes. We report the existence of a total of 27 gcy genes encoding receptor-type guanylyl cyclases and of 7 gcy genes encoding soluble guanylyl cyclases in the complete genome sequence of C. elegans. We describe the expression pattern of all previously uncharacterized receptor-type guanylyl cyclases and find them to be highly biased but not exclusively restricted to the nervous system. We find that >41% (11/27) of all receptor-type guanylyl cyclases are expressed in the ASE gustatory neurons and that one-third of all gcy genes (9/27) are expressed in a lateral, left/right asymmetric manner in the ASE neurons. The expression of all laterally expressed gcy genes is under the control of a gene regulatory network composed of several transcription factors and miRNAs. The complement of gcy genes in the related nematode C. briggsae differs from C. elegans as evidenced by differences in chromosomal localization, number of gcy genes, and expression patterns. Differences in gcy expression patterns in the ASE neurons of C. briggsae arise from a difference in cis-regulatory elements and trans-acting factors that control ASE laterality. In sum, our results indicate the existence of a surprising multitude of putative chemoreceptors in the gustatory ASE neurons and suggest the existence of a substantial degree of laterality in gustatory signaling mechanisms in nematodes.

Alleles↗

The fracture of the proximal end of the radius in adolescence.

According to a follow-up of 50 fractures of the proximal end of the radius in adolescence the cause and prevention of later persisting functional disturbances, posttraumatic valgisation of the elbow axis and posttraumatic growth disturbances are investigated. Furthermore, the limitations of spontaneous correction of malposition in this area during further growth should be defined. Contrary to current opinion prevailing till now in the literature, not the primary tilt, but the performed therapy turned out to be the cause for later functional disturbance: we found significantly more frequently functional restriction of pro-supination after closed or open repositions than after primary casts without any reposition. The primary malposition of the fracture has no influence on this result just as little as the remaining malposition at consolidation. Furthermore, we noted that the spontaneous correction of malposition in further growth is far more than assumed up to now: all still noticeable malpositions at consolidation up to maximum 65 degrees were corrected again spontaneously in further growth. The posttraumatic valgisation of the elbow axis showed no dependence most of all upon therapy or malposition. According to the results we recommend the following therapeutical procedure for this fracture, using to the full the correcting forces of the growing skeleton, noe performing any reposition, neither closed nor open. With that, the posttraumatic disturbance of nutrition of the proximal end of the radius should be kept to a minimum, furthermore the frequency and extent of the restriction of prosupination diminished resp. avoided. For tilts over 60 degrees as well as displacements and latus over half the width of the shaft we recommend open reposition, if possible without any fixation.

Adolescent↗

[An immunohistochemical study of distribution of insulin in lateral pterygoid muscle after functional mandibular protrusion in rats].

OBJECTIVE: The aim of this study is to investigate the effects of insulin on the lateral pterygoid muscle of growing rats after the functional mandibular protrusion. METHODS: An immunohistochemical (the ABC method) method was used to detect the location and distribution of insulin in the lateral pterygoid muscle of rats. RESULTS: 1. Insulin located in the cell membrane of the lateral pterygoid muscle. 2. The distribution of insulin in the lateral pterygoid muscle of rats was enhanced after the functional mandibular protrusion. CONCLUSION: Insulin may play an important role in adaptive remodeling of the lateral pterygoid muscle after the treatment of functional mandibular protrusion.

Animals↗

Lateralized anterior mesiotemporal lobe activation: semirandom functional MR imaging encoding paradigm in patients with temporal lobe epilepsy--initial experience.

PURPOSE: To prospectively demonstrate anterior mesiotemporal lobe (MTL) activation in healthy volunteers by using a semirandom memory-encoding paradigm and to prospectively compare lateralized functional magnetic resonance (MR) imaging activation with intracarotid amobarbital procedure (IAP) memory test results in patients with temporal lobe epilepsy (TLE) who were scheduled to undergo surgery. MATERIALS AND METHODS: The study was approved by a local ethics committee, and written informed consent was obtained from all subjects. Eight healthy volunteers and 18 patients with TLE who were scheduled for surgery were included in the functional MR imaging study involving the use of a memory-encoding paradigm with variable epoch lengths. Subjects were instructed to memorize new pictures that were mixed among pictures that they had seen before. Data analysis entailed computations of the contrast between the MTL activation induced by the new pictures and the MTL activation induced by the old pictures and of the lateralization index, defined as the relative difference in the number of activated voxels between the left and right MTLs. Lateralization indexes were compared between the patients and the volunteers and statistically correlated with the patients' IAP memory test results. To study deviations from perfect correspondence between the functional MR imaging- and IAP-derived lateralization indexes, orthogonal regression analysis was applied. Proportional relations for the patients with left-sided TLE and for those with right-sided TLE were calculated separately. RESULTS: The memory paradigm consistently activated the posterior and anterior MTL structures in both the healthy volunteers and the patients. Regression analysis revealed that functional MR imaging activation was stronger than the IAP results when it was lateralized to the contralateral MTL. This analysis also revealed a significant (P < .001) correlation between the functional MR imaging results and the IAP results in the patients with right-sided TLE but not in those with left-sided TLE (P > .1). CONCLUSION: The functional MR imaging memory-encoding paradigm consistently yielded MTL activation in the volunteers and the patients with TLE, but lateralized functional MR imaging activation was in concordance with the IAP results in only those patients with right-sided TLE.

Adult↗

The neuropsychological significance of lateral preference for complex visual activities in children with learning disabilities.

In the present study the relationship between neuropsychological functioning and lateral preference for visual activities was examined with learning disordered children. Specifically, the relationship between measures of the Lateral Dominance Exam (LDE), scores on the Halstead-Reitan Neuropsychological Battery (HRNB), and the Wechsler Intelligence Scale for Children-Revised (WISC-R) were explored. A canonical analysis suggested that composites of neuropsychological functioning and lateral preference shared 22% of variance. Learning disabled children with strong right or left preference for visually guided motor activities showed lower performance in spatial tasks on the ipsilateral side and in simple motor skills on the contralateral side. Children in the present study with strong right preference patterns for visually assisted motor activities also showed low performance on visual tracking tasks. These data offer some support for assessing lateral preference in learning disabled children.

Adolescent↗

[Incidence of intra-individual lateral differences in interference fringe acuity and entoptic functions and their prognostic value with reference to lateral differences in optotypic acuity].

No adequate research results are available on the frequency and medical significance of intraindividual side differences in the entoptic functions and interference fringe acuity. We have collected data on these topics from examinations of 312 people with no eye defects; the subjects in this group were aged between 6 and 85 years and were divided into ten age-groups of approximately the same size. We were trying to find out to what extent a real side difference in the distant or near visual acuity can be deduced from an intraindividual side difference in the entoptic function test and/or laser interferometry as in healthy people. To allow grading of macular chagrin patches for the first time we defined the "microsymptoms of macular chagrin" patches. Moreover, we described the changes in interference fringe acuity and in entoptic function with advancing age. By using already established research approaches, we have evaluated the following parameters of examination: distant visual acuity with optotypes, near visual acuity (Nieden), entoptic functions (vessel figure of Purkinje and macular chagrin patches), laser interferometry (Retinometer) and ophthalmological findings. We found that of macular chagrin varied in appearance with the age of the patient. Patients with no eye defects seldom have an intraindividual side difference in the distant or near visual acuity, and any present is only marginal. This is why there seems to be too narrow a correlation with the results of the laser interferometry and of the entoptic function test. The negative predictive value is between 89% and 95%. This means that patients who have no side difference in interference fringe acuity or in the entoptic function test also have no intraindividual side difference in distant visual acuity with optotypes or near visual acuity (Nieden). This is the medical significance of our results in respect to more marked side differences such as are found in patients with eye defects. The predictive significance of the entoptic function test is enhanced by knowledge of microsymptoms of macular chagrin patches.

Accommodation, Ocular↗

Ultrastructural changes of mitochondria in the skeletal muscle of patients with amyotrophic lateral sclerosis.

Functional defects and morphological changes of mitochondria have been reported to be in the skeletal muscle of patients with amyotrophic lateral sclerosis (ALS). Recent studies suggested that mitochondrial abnormalities are related to the pathogenesis of ALS. The purpose of this study is to evaluate the ultrastructural changes of muscle mitochondria in ALS patients. The authors examined 49 cases of diagnostic muscle biopsy samples with definite or probable ALS by electron microscopy. Of the 49 cases, 5 (10%) had ultrastructural abnormalities of muscle mitochondria, including giant mitochondria, paracrystalline inclusions, and abnormal cristae. These abnormal mitochondria were mainly observed among subsarcolemmal mitochondrial aggregates.

Adult↗

Effects of lateral recumbency on regional lung function in anesthetized horses.

Six horses were anesthetized and placed in lateral recumbency for 1 hour and then were turned to the opposite side for an additional hour. A short-lived radioactive gas, 81mKr, was used to determine the relative spatial distribution of ventilation (V) and perfusion (Q) in these horses. Effects of time, side down, and turning on the distribution were evaluated. A consistent gradient of V/Q was found at all times, with the highest V/Q values at the top (non-dependent) portion of the lung field and the lowest at the bottom (dependent). This gradient was also present within each lung, as well as between lungs. Effects of time were not observed. Horses starting in right lateral recumbency had larger gradients of V/Q than did those starting on the left. The gradient decreased after turning in both groups. After turning, the gradients in the right lung were again greater han those in the left lung.

Anesthesia, General↗

Cerebral specialization and interhemispheric communication: does the corpus callosum enable the human condition?

The surgical disconnection of the cerebral hemispheres creates an extraordinary opportunity to study basic neurological mechanisms: the organization of the sensory and motors systems, the cortical representation of the perceptual and cognitive processes, the lateralization of function, and, perhaps most importantly, how the divided brain yields clues to the nature of conscious experience. Studies of split-brain patients over the last 40 years have resulted in numerous insights into the processes of perception, attention, memory, language and reasoning abilities. When the constellation of findings is considered as a whole, one sees the cortical arena as a patchwork of specialized processes. When this is considered in the light of new studies on the lateralization of functions, it becomes reasonable to suppose that the corpus callosum has enabled the development of the many specialized systems by allowing the reworking of existing cortical areas while preserving existing functions. Thus, while language emerged in the left hemisphere at the cost of pre-existing perceptual systems, the critical features of the bilaterally present perceptual system were spared in the opposite half-brain. By having the callosum serve as the great communication link between redundant systems, a pre-existing system could be jettisoned as new functions developed in one hemisphere, while the other hemisphere could continue to perform the previous functions for both half-brains. Split-brain studies have also revealed the complex mosaic of mental processes that participate in human cognition. And yet, even though each cerebral hemisphere has its own set of capacities, with the left hemisphere specialized for language and speech and major problem-solving capacities and the right hemisphere specialized for tasks such as facial recognition and attentional monitoring, we all have the subjective experience of feeling totally integrated. Indeed, even though many of these functions have an automatic quality to them and are carried out by the brain prior to our conscious awareness of them, our subjective belief and feeling is that we are in charge of our actions. These phenomena appear to be related to our left hemisphere's interpreter, a device that allows us to construct theories about the relationship between perceived events, actions and feelings.

Animals↗

Lateral biases for holding infants: early opinions, observations, and explanations, with some possible lessons for theory and research today.

In 1962, the psychologist Lee Salk reported finding that 80% of mothers held their infants on the left side of their body, so that the infant's head was to their left. Salk's finding has been amply confirmed, with new studies of mothers as well as other adults reporting figures for left-side holding ranging from 60 to 85% (e.g., de Chateau, 1983; Harris & Fitzgerald, 1985; Harris, Almerigi, & Kirsch, 2000). New studies also suggest that the bias is only for holding infants (or infant dolls), not for books, packages, or other objects (e.g., Almerigi, Carbary, & Harris, 2001; Rheingold & Keene, 1965). The possibility that it is unique to infants (or their likenesses) is what gives it special interest for investigators who study laterality of function. The discovery of the bias is often credited to Salk, but it would be more accurate to say that he rediscovered it because it was first noted at least two hundred years earlier, then, evidently, forgotten, only to be rediscovered and again forgotten several times through the early decades of the twentieth century. Over this period, however, not all agreed that the preferred side was the left: a nearly equal number said it was the right. Each group also proposed explanations for why one or the other side was preferred. They also foresaw different consequences for the infant being held. In the 1980s, I briefly described some of the early reports in essays on the history of theories and research on laterality of function (Harris, 1980, 1983). A manuscript now in preparation provides a more comprehensive description and evaluation of these reports and suggests certain lessons they may hold for current theory and research. The poster proposed for TENNET XII will summarize the main points of this new review and analysis. The poster will be organized into 6 sections, with bulleted text accompanied by drawings, photographs, and other illustrations. The plan is to make the story as visual as possible.

Brain↗

The distribution of functional impairment across the lateral border of acutely ischemic myocardium.

To evaluate the degree and lateral extent of dysfunction in nonischemic myocardium adjacent to ischemic muscle, we measured systolic wall thickening with sonomicrometers during circumflex coronary occlusion in 12 anesthetized, open-chest dogs. The locations of the wall thickness measurements relative to the perfusion boundary were determined with myocardial blood flow (microspheres) maps constructed from multiple, small tissue samples. Five minutes after circumflex occlusion, systolic wall thickening in the central ischemic zone decreased from 3.00 +/- 0.61 (mean +/- SD) mm to -0.61 +/- 0.36 mm (P less than 0.01). In nonischemic myocardium greater than 10 mm from the perfusion boundary, systolic wall thickening increased from 2.56 +/- 0.57 to 3.24 +/- 0.72 mm (P less than 0.01). In nonischemic myocardium within 10 mm of the perfusion boundary, systolic wall thickening was slightly but significantly reduced compared with control (2.72 +/- 0.80 to 2.44 +/- 0.79 mm, P less than 0.05), supporting the concept of regional dysfunction in nonischemic myocardium at the lateral borders of an ischemic area. Sigmoid curves were fitted to the data to model changes in wall thickening as a continuous function of distance from the perfusion boundary. This allowed estimation of the extent of dysfunction into nonischemic myocardium which averaged less than 8 mm (approximately 30 degrees of endocardial circumference) at one border. The level of functional impairment in this zone was relatively modest, and systolic wall thickening in the immediate border area was reduced more than 50% from control only in tissue characterized by a blood supply of mixed ischemic and nonischemic origin. We conclude that a functional border zone exists lateral to an acutely ischemic area, but measurement of regional function produces relatively small exaggeration of the size of the acutely ischemic zone if severe reduction in mechanical performance is used to define the extent of the ischemic area.

Acute Disease↗