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Sequence analysis of the fiber genomic region of a porcine adenovirus predicts a novel fiber protein.

The complete nucleotide sequence of the putative fiber protein of a porcine adenovirus isolate, NADC-1, was determined. The coding sequence for the fiber protein was found to be 2112 nucleotides, predicting a 703 amino acid protein with a calculated molecular mass of 76,681 Da. The coding sequence is located between 86 and 92.5 map units. A polyadenylation signal was found 44 bases downstream of the stop codon. Northern hybridization analysis identified a band at 2.4 kb, which likely includes the primary transcript plus a tripartite leader (typically found with adenovirus transcripts) and a polyA(+) tail. The predicted NADC-1 fiber protein was found to have a tail domain comparable in size and sequence to most adenovirus fiber proteins, a comparatively short shaft region, and a head region that was more than twice as large as that of other adenovirus fiber proteins. Each of the three structural domains (tail, shaft, and head) of the predicted NADC-1 fiber protein was found to be most similar to the corresponding domain of a different mammalian adenovirus. The NADC-1 fiber head contained an RGD sequence, a motif that is found in the penton protein of other adenoviruses. Furthermore, the predicted amino acid sequence of the C-terminal half of the NADC-1 fiber head has significant homology to S-lectin proteins, a characteristic not shared with other adenovirus fiber proteins. Thus the predicted amino acid sequence of the NADC-1 fiber head is unique among adenoviruses for which the sequence of the fiber protein is known.

Amino Acid Sequence↗

The role of fiber-matrix interactions in a nonlinear fiber-reinforced strain energy model of tendon.

The objective of this study was to develop a nonlinear and anisotropic three-dimensional mathematical model of tendon behavior in which the structural components of fibers, matrix, and fiber-matrix interactions are explicitly incorporated and to use this model to infer the contributions of these structures to tendon mechanical behavior. We hypothesized that this model would show that: (i) tendon mechanical behavior is not solely governed by the isotropic matrix and fiber stretch, but is also influenced by fiber-matrix interactions; and (ii) shear fiber-matrix interaction terms will better describe tendon mechanical behavior than bulk fiber-matrix interaction terms. Model versions that did and did not include fiber-matrix interaction terms were applied to experimental tendon stress-strain data in longitudinal and transverse orientations, and the R2 goodness-of-fit was evaluated. This study showed that models that included fiber-matrix interaction terms improved the fit to longitudinal data (R2(toe) = 0.88, R2(Lin) = 0.94) over models that only included isotropic matrix and fiber stretch terms (R2(Toe) = 0.36, R2(Lin) = 0.84). Shear fiber-matrix interaction terms proved to be responsible for the best fit to data and to contribute to stress-strain nonlinearity. The mathematical model of tendon behavior developed in this study showed that fiber-matrix interactions are an important contributor to tendon behavior The more complete characterization of mechanical behavior afforded by this mathematical model can lead to an improved understanding of structure-function relationships in soft tissues and, ultimately, to the development of tissue-engineered therapies for injury or degeneration.

Animals↗

Reduction of natural adenovirus tropism to the liver by both ablation of fiber-coxsackievirus and adenovirus receptor interaction and use of replaceable short fiber.

The initial recognition and binding of adenovirus vector to the host cell surface is mediated by interaction between the adenovirus fiber knob protein and its receptor, the coxsackievirus and adenovirus receptor (CAR). This natural tropism of adenovirus vector needs to be ablated in order to achieve targeted gene transfer. To this end, we noted that adenovirus serotype 40 (Ad40) contains two distinct long and short fibers; the short fiber is unable to recognize CAR, while the long fiber binds CAR. We generated adenovirus serotype 5-based mutants with chimeric Ad40-derived fibers, which were composed of either long or short shafts together with CAR binding or nonbinding knobs. The capacity of these adenovirus mutants for in vitro and in vivo gene transfer to liver cells was examined. In the case of primary human hepatocytes displaying a high expression level of CAR and alphav integrin, both CAR binding ability and fiber shaft length played important roles in efficient transduction. Most significantly, the high transduction efficiency observed in the liver and spleen following intravenous administration of adenovirus vector was dramatically reduced by both ablation of fiber-CAR interaction and the use of replaceable short fiber. In other tissues displaying a low level of transduction, no significant differences in transduction efficiency were observed among adenovirus vector mutants. Furthermore, incorporation of a 7-lysine-residue motif at the C-terminal end of CAR-nonbinding short fiber efficiently achieved transduction of target cells via the heparan-containing receptor. Our results demonstrated that the natural tropism of adenovirus in vivo is influenced not only by fiber-CAR interaction but also by fiber shaft length. Furthermore, our strategy may be useful for retargeting adenovirus to particular tumors and tissue types with specific receptors.

Adenoviridae↗

Influence of fiber type and muscle source on Ca2+ sensitivity of rat fibers.

This study investigated the influence of muscle source and fiber type on the calcium sensitivity of skinned rat skeletal muscle fibers from predominantly slow muscles [soleus (SOL) and adductor longus (AL)], mixed muscle [posterior gracilis (PG)], and predominantly fast-twitch muscle [extensor digitorum longus (EDL)]. Fibers were characterized histochemically and by one-dimensional protein gel electrophoresis, and calcium-tension relationships were determined. Fiber type and muscle source had significant effects on the negative log of the calcium concentration associated with half-maximal tension (pCa1/2). Slow-twitch fibers had larger values of pCa1/2 than did fast-twitch fibers. Slow-twitch fibers from the predominantly slow muscles, SOL and AL, had similar values of pCa1/2 but slightly smaller values than from the mixed muscle, PG. Fast-glycolytic (FG) fibers from the predominantly fast muscle, EDL, had a higher pCa1/2 than fibers from the mixed fiber type muscle, PG. There were no differences between the pCa1/2 associated with FG and fast-oxidative-glycolytic fibers.

Adenosine Triphosphatases↗

Muscle fiber formation and fiber hypertrophy during the onset of stretch-overload.

The contributions of fiber hypertrophy and new fiber formation to the onset of stretch-induced muscle enlargement were evaluated in the anterior latissimus dorsi (ALD) of adult Japanese quails, because it was not known whether the mechanisms which initiate new fiber formation were dependent on first achieving significant fiber hypertrophy. A weight corresponding to 10% of the bird's body mass was attached to one wing, and eight birds were killed after each day during the first week of stretch. Muscle mass was significantly increased after 48 h of stretch; however, the elevation in nonmuscle tissue accounted for this increase. Muscle mass corrected for non-muscle tissue was significantly greater than the intra-animal control by the fourth day of stretch. Mean fiber cross-sectional area did not change during days 0-6, but cross-sectional area was 30.0 +/- 17.2% greater than the intra-animal control areas at day 7. Fiber number determined after nitric acid digestion of connective tissue was 27.1 +/- 5.8% greater than the intra-animal control at days 5-7 of stretch, but the number of fibers in the control muscles at days 5 and 6 were lower than at day 0. Thus new fiber formation was not preceded by significant fiber hypertrophy. These results fail to support a mechanism for new fiber formation which involves fiber splitting from hypertrophied myofibers during the first week of stretch.

Animals↗

Histochemical and molecular determination of fiber types in chemically skinned single equine skeletal muscle fibers.

Until now, there has been no reliable method for histochemical determination of fiber types of single skinned muscle fibers. The major problem arises from the fact that most histochemical techniques use cross-sections of a large group of fibers and compare a given fiber with those surrounding it. This is not possible with a single skinned fiber which has been separated from a bundle to be used for mechanical analysis. A further problem is that the skinning procedure itself may alter the staining pattern. We have developed a procedure by which multiple cross-sections of single skinned fibers can be exposed to various histochemical reactions and the staining patterns compared on the same slide to those of frozen muscle and skinned bundles. By this procedure, three fiber types were distinguished by both Ca2+-ATPase and SDH reactions. The fiber typings determined from both enzyme systems correlated well with each other. Although we were able to differentiate only between slow and fast fibers by SDS-PAGE, these results corroborated the histochemical classification. This procedure will clearly be useful in skinned single muscle fiber mechanics experiments performed to determine functional differences among fiber types.

Animals↗

Reactive oxygen metabolite production induced by asbestos and glass fibers: effect of fiber milling.

Particle stimulated chemiluminescence (CL) production by human polymorphonuclear leucocytes (PMN) has been utilized to evaluate the pathogenicity of mineral and glass fibers with the understanding that reactive oxygen metabolites (ROM) production as measured by CL is etiopathogenically related to fiber toxicity. In the present study to investigate the specific pathogenic role of fiber number and dimensions, CL production from PMN exposed to anthophyllite asbestos mineral and glass fiber samples milled for different time periods was measured. Almost all the fibrous particles in the glass fiber sample were destroyed after milling for 30 minutes. With anthophyllite, the total number of fibrous particles remained almost constant for up to 240 minutes of milling, although the size of fibrous particles was reduced. CL produced by the same mass of glass fiber was elevated after milling for 15 minutes, but then declined when the milling time was further increased. Similarly, with anthophyllite, the production of CL was elevated at the first period of milling for 30 minutes, but then declined at the longer milling times. The level of CL produced was not correlated to the total number of fibrous particles, for both the glass fiber and the anthophyllite samples. Likewise for the glass fiber and anthophyllite samples, no specific range of fiber dimension was correlated to the peak hight CL production. These findings indicate that neither the total number, nor the specific range of fiber dimension solely determines CL production. As a consequence, it may be concluded that other physiochemical factors, such as the surface reactive characteristics of milled fibers, may be more closely related to CL production by PMN.

Air Pollutants, Occupational↗

Influence of the fiber length on the power spectra of single muscle fiber extracellular potentials.

Influence of the fiber length on the power spectra of the single muscle fiber extracellular action potentials (SMFEAPs) as well as on the spectral changes under alterations in the propagation velocity (v) and intracellular action potential duration (Tin) was studied theoretically for a fiber-electrode distance typical of surface recordings. It was shown that the magnitude and distribution of the SMFEAP spectral power depend on the fiber length. The shorter the fiber, the wider the frequency region in which the total spectral power is distributed and the smaller the spectrum max amplitude. The fiber length affects the spectrum changes that are due to alterations in v or Tin, and, consequently, the spectrum characteristic frequencies--Fmax, Fmed and Fmean, as well as the total spectral amplitude (TSA) and total power (TP). Whereas for a relatively long fiber Fmax depends linearly on v and Fmed and Fmean increase with v increasing, for a short fiber the linearity of the relation between Fmax and v can be disturbed, and Fmed and Fmean can decrease with v increasing. Under the condition of a relatively short fiber, a change in Tin can cause changes not only in Fmed and Fmean, but in Fmax as well. It was shown, that as a result of the finite length of the muscle fibers as well as of the asymmetry of the end-plate location in relation to the fiber ends, dips can be observed in the spectrum even in a case of monopolar recording. Positions of the dips in the power spectra depend on propagation velocity.

Action Potentials↗

[Correlations between feet posture and muscle fiber size in mammals--comparison of the anterior tibial muscle fiber among plantigrade type, digitigrade type and unguligrade type].

The size (micron2) of red muscle fibers (Type 1), white muscle fibers (type 2) and intermediate muscle fibers (type 3) was quantitatively determined in cross-sectional areas of the venter of the anterior tibial muscle in the plantigrade type, digitigrade type and unguligrade type using 122 individuals of 15 species in 5 orders, and correlations between the type of locomotion and muscle fiber size were analyzed from a comparative anatomical viewpoint. Regardless of species, red muscle fibers with slow contraction were small in diameter, intermediate muscle fibers (which are believed to have characteristics of both types 1 and 2) were intermediate in diameter, and white muscle fibers with fast contraction were large in diameter. Muscle fiber size (types 1 through 3) was largest in the orangutan, followed by the brown bear, rat, crab-eating monkey and human, in that order, in the plantigrade type. The size was intermediate in the goat, pig and horse in the unguligrade type, and white-handed gibbon, chimpanzee and rabbit in the plantigrade type. The size was relatively small in the cat, dog, Japanese raccoon dog and Japanese for in the digitigrade type within the same species, muscle fiber size increased in proportion to the increase in body weight. However, there was no correlation between body size and muscle fiber size among different species. The above results suggest that muscle fiber size in the mammalian leg is regulated by anatomical morphology, i.e., plantigrade, digitigrade and unguligrade types, and shows individual adaptive variation.

Animals↗

Effect of anodal blockade of myelinated fibers on vagal C-fiber afferents.

The effects of monopolar cathodal, monopolar anodal, and bipolar anodal polarizing currents on vagal A- and C-fiber activity were studied in anesthetized dogs. Monopolar cathodal polarization consistently produced excitation of spontaneous and evoked A- and C-fibers. Monopolar anodal and bipolar anodal polarizations differentially blocked A-fibers as a function of fiber diameter. The specific purpose of this study was to compare the effects of monopolar anodal and bipolar anodal currents on C-fiber excitability. Small fiber preparations were dissected from the vagal trunk, cut centrally, and placed on recording electrodes. A constant-current stimulus pulse was applied to the nerve at various distances from the blocking electrodes. The stimulus current strength was increased until an isolated C-fiber spike was observed. This value was defined as 100% of threshold. The stimulus current was then reduced to zero, the blocking current was increased slowly to 100 microA, and the procedure repeated. Threshold data obtained in this manner for each set of stimulation electrodes was plotted as a function of distance from the blocking electrode(s) for both modes of anodal blockade. No significant change in C-fiber excitability was observed with bipolar anodal blockade, whereas excitability was significantly (P less than or equal to 0.05) decreased using the monopolar technique. Thus, monopolar anodal block may reduce the possibility of asynchronous C-fiber discharge, which has been associated with a bipolar block of A-fibers.

Afferent Pathways↗

The topographic organization of associational fibers of the olfactory system in the rat, including centrifugal fibers to the olfactory bulb.

This study analyzed the topographic organization of the associational fibers within the olfactory cortex of the rat, by using the autoradiographic method. Small injections of 3H-leucine were placed in all of the subdivisions of the olfactory cortex, to label selectively the fibers arising in each area. Intracortical fibers were identified from all of the olfactory cortical areas except the olfactory tubercle and were classified into two major systems (the layer Ib system and the layer II-deep Ib system) on the basis of their laminar pattern of termination (see Luskin and Price, '83). The layer Ib fiber system arises in the anterior olfactory nucleus, piriform cortex, and lateral entorhinal area, and is broadly organized in relation to the lateral olfactory tract. Cortical areas deep to or near the lateral olfactory tract are preferentially interconnected with areas near the tract, while parts of the cortex lateral and caudal to the lateral olfactory tract are most heavily interconnected with areas lateral, caudal, and medial to the tract. Commissural projections from the anterior olfactory nucleus and the anterior piriform cortex match some (but not all) components of the ipsilateral layer Ib fiber system. The layer II-deep Ib fiber system arises in three small areas--the ventral tenia tecta, the dorsal peduncular cortex, and the periamygdaloid cortex. The fibers from the ventral tenia tecta terminate in layer II of the anterior olfactory nucleus and are topographically organized. The fibers from the dorsal peduncular cortex and the periamygdaloid cortex are more widely distributed, especially in the lateral and caudal parts of the cortex. Two other intracortical projections do not fit into either of these fiber systems. The nucleus of the lateral olfactory tract projects bilaterally to the islands of Calleja and the medial edge of the anterior piriform cortex. The anterior cortical nucleus projects to many parts of the olfactory cortex, but the fibers end in both superficial and deep parts of layer I (layer Ia and Ib). There are projections from several of the olfactory cortical areas to the cortical areas surrounding the olfactory cortex. Virtually all of the olfactory areas also project to the ventral and dorsal endopiriform nuclei deep to the piriform cortex and/or to the polymorph zone deep to the olfactory tubercle. In addition, projections have been demonstrated to the deep amygdaloid nuclei, especially from the more ventromedial and caudal parts of the olfactory cortex.

Amygdala↗

Fiber-type compositions in postnatal chicken muscle spindles with low intrafusal fiber counts and their developmental significance.

The fiber-type composition of postnatal chicken leg muscle spindles with from one to four intrafusal fibers was examined in sections incubated with monoclonal antibodies against fast and slow myosin heavy chains. In monofibral spindles the lone intrafusal fiber was almost always fast. In duofibral spindles usually one slow and one fast fiber were present. Trifibral spindles most often displayed two fast and one slow fiber, whereas quadrofibral receptors characteristically contained two slow and two fast fibers. Earlier results showed that the primary intrafusal myotube in nascent spindles has almost always a fast myosin heavy chain profile and that the proportion of slow myotubes and fibers increases as intrafusal fiber bundles grow in size. Data from postnatal chicken leg muscles collected here suggest that up to the first four fibers this proportional increase can be largely accounted for if consecutive intrafusal fibers arise in a fast-slow-fast-slow sequence. The late recognition during myogenesis of primary intrafusal myotubes and their fast myosin heavy chain profiles warrant exploring if nascent chicken muscles spindles are first seeded by fast fetal myoblasts.

Animals↗

Fiber type and fiber size of cat ankle, knee, and hip extensors and flexors following low thoracic spinal cord transection at an early age.

Effects of low thoracic spinal transection on muscle weights, fiber type distributions, and fiber cross-sectional areas (CSAs) of selected cat hind limb mixed-fast flexors and extensors and slow extensors were studied. Cats were spinalized at T12 at 2 weeks of age and maintained for 6 to 12 months. In general spinalization resulted in a decrease in muscle weights of extensors, while the weights of those muscles that function as either flexors or as both flexors and extensors were maintained. The percentages of fast-twitch [fast glycolytic (FG) and fast oxidative-glycolytic (FOG)] fibers increased and slow oxidative (SO) fibers decreased as a result of spinalization. However, FG fibers had a smaller CSA after spinal transection in both extensors and flexors. The total relative CSA of FG fibers per whole muscle was similar in spinalized and control cats. The relative muscle CSA occupied by SO fibers decreased in extensors and flexors as a result of a lower proportion of SO fibers and/or smaller SO fibers in spinalized cats. These findings suggest that muscles become more "fast-like" histochemically while little change occurs in the oxidative staining properties in either extensors or flexors in 6- to 12-month-old cats transected at 2 weeks of age. Further, these data suggest that the amount of muscle atrophy that occurs as a result of spinal transection is not closely related to the percentage reduction in SO fibers.

Animals↗

Coding of stimulus location and intensity in populations of mechanosensitive nerve fibers of the raccoon: I. Single fiber response properties.

The primary aim of this study was to determine and compare the receptive field (RF) characteristics and response properties of single mechanosensitive nerve fibers innervating the glabrous skin of the forepaw and hindpaw of the raccoon. The action potentials of 129 median nerve fibers and 61 posterior tibial nerve fibers were recorded in response to punctate mechanical stimuli varying in location and intensity. The stimuli were delivered to six standard test sites on digit 1 and the contiguous pads of each paw. Attempts were made to classify each fiber according to its rate of adaptation to sustained stimulation; the RF of each fiber was mapped using a standard series of stimulus intensities. The results indicated that the response properties of individual fibers were highly complex and depended on the location and intensity of stimulation. 1) The distributions of absolute threshold were not different for the median or tibial nerve fibers or for different classes of fibers based on adaptation rate. A distal to proximal increase in threshold was found for each paw, suggesting a corresponding gradient of sensitivity across the glabrous skin. 2) Threshold RF areas did not vary across either paw nor did they differ between the two paws. Suprathreshold RFs were quite large relative to expected tactile acuity and displayed complex features. 3) Response properties such as adaptation rate, on- and off-responses, were found to vary with both stimulus location and intensity. It was concluded that the responses of individual nerve fibers could not uniquely encode any stimulus parameter tested, and that the properties of single fibers could not account for apparent differences in tactile acuity across each paw or between the two paws.

Action Potentials↗

Abeta-fiber nociceptive primary afferent neurons: a review of incidence and properties in relation to other afferent A-fiber neurons in mammals.

The existence of nociceptors with Abeta-fibers has often been overlooked, and many textbooks endorse the view that all nociceptors have either C- or Adelta-fibers. Here we review evidence starting from the earliest descriptions of A-fiber nociceptors, which clearly indicates that a substantial proportion of cutaneous/somatic afferent A-fiber nociceptors conduct in the Abeta conduction velocity (CV) range in all species in which CV was carefully examined, including mouse, rat, guinea pig, cat and monkey. Reported proportions of A-fiber nociceptors with Abeta-fibers vary from 18% to 65% in different species, usually >50% in rodents. In rat, about 20% of all somatic afferent neurons with Aalpha/beta-fibers were nociceptive. Distributions of CVs of A-fiber nociceptors usually appear unimodal, with a median/peak in the upper Adelta or lower Abeta CV range. We find no evidence to suggest discontinuous differences in electrophysiological or cytochemical properties of Adelta and Abeta nociceptors, rather there are gradual changes in relation to CV. However, some functional differences have been reported. In cat, A-fiber nociceptors with lower mechanical thresholds (moderate pressure receptors) tend to have faster CVs [P.R. Burgess, D. Petit, R.M. Warren. Receptor types in cat hairy skin supplied by myelinated fibers. J. Neurophysiol. 31 (1968) 833-848]. In primate (monkey) A-fiber nociceptors that responded to heat were divided into type I A mechano-heat (AMH) units (Adelta and Abeta CVs) with lower mechanical and higher heat thresholds and may include moderate pressure receptors, and type II AMH units (Adelta CVs) with higher mechanical/lower heat thresholds. It is important that the existence of Abeta nociceptors is recognised, because assumptions that fast conducting, large diameter afferents are always low threshold mechanoreceptors might lead/have led to misinterpretations of data.

Afferent Pathways↗

Differential in vitro cellular response induced by exposure to synthetic vitreous fibers (SVFs) and asbestos crocidolite fibers.

In this study, we analyzed the effects of synthetic vitreous fibers (SVFs) on a mesothelial (MeT5A) and a fibroblast cell line (NIH3T3), compared to those exerted by crocidolite asbestos fibers. SVFs (glass wool, rock wools) do not induce significant changes in cell mortality, whereas crocidolite asbestos fibers caused a dose-dependent cytotoxicity. We investigated the correlation between the fiber-induced cytotoxicity and the extent and type of interaction of the fibers with the cell surface, and we observed that SVFs, unlike crocidolite asbestos fibers, establish few and weak interactions. Moreover, after internalization, crocidolite asbestos fibers are often found free in the cytoplasm, whereas glass wool fibers are mainly localized inside cytoplasmic vacuoles. After treatments, we also detected signs of oxidative stress, revealed by an increased reactive oxygen species (ROS) production and by an induction of superoxide dismutase (SOD) activity. The lipoperoxidative damage was characterized by a decrease in polyunsaturated fatty acids (PUFA), an increase in the content of thiobarbituric reactive species (TBARS) and a consumption of vitamin E, as a lipophilic antioxidant. Furthermore, we investigated the effect of fiber exposure on cell proliferation. and it was found that, unlike crocidolite asbestos fibers, SVFs did not induce a significant increase in DNA synthesis.

Animals↗

Is fiber satiating? Effects of a high fiber preload on subsequent food intake of normal-weight and obese young men.

This study was designed to test whether a high fiber preload can suppress food intake at a subsequent test meal. Fifty male undergraduates, 31 of normal body weight and 19 at least 15 per cent overweight, participated as paid volunteers. So as not to inhibit spontaneous food intake, they were told that the investigators were studying the effects of the parasympathetic nervous system on cognitive processes and they were given a picture rating task to perform. The stated rationale for having the subjects eat the preload between two sets of pictures was to alter the state of parasympathetic activation. The preload consisted of two roast beef sandwich halves containing a total of 400 kcal and either 5.2 or 0.2 g of crude fiber in the bread. The preload was eaten by the subjects, their meal was intentionally interrupted and then they were allowed to finish eating 30-45 minutes later (test meal). Obese subjects ate significantly fewer sandwich halves after the high than after the low fiber preload. Obese subjects ate significantly more than non-obese subjects in the low fiber treatment so that the effect of the high fiber was to normalize their intake. Although both obese and normal-weight subjects reported feeling fuller after the high fiber preload, the non-obese subjects ate virtually the same amount in both treatments. Obese subjects reported liking the high fiber bread less well than the low fiber bread but additional statistical analyses showed an intake-suppressing effect of fiber even after controlling for bread rating. These results support the hypothesis that fiber reduces caloric intake in obese people.

Adult↗

Selective age-related degradation of anterior callosal fiber bundles quantified in vivo with fiber tracking.

The corpus callosum, the principal white matter structure enabling interhemispheric information transfer, is heterogeneous in its microstructural composition, heterotopic in its anteroposterior cortical connectivity, and differentially susceptible to aging. In vivo characterization of callosal features is possible with diffusion tensor imaging (DTI), a magnetic resonance imaging method sensitive to the detection of white matter's linear structure. We implemented a quantitative fiber tracking approach to examine age-related variation in regional microstructural characteristics [fractional anisotropy (FA) and apparent diffusion coefficient (ADC)] of callosal fibers in 10 younger (29 +/- 5 years) and 10 older (72 +/- 5 years) healthy adults. Fiber tracking was performed on 2.5 mm isotropic voxels collected at 3 T. Fiber targets comprised the midsagittal corpus callosum, divided into six regions based on known callosal anatomical projections. FA and ADC for each voxel of each fiber identified were determined; lower FA and higher ADC reflect degraded microstructural tissue integrity. Older subjects had lower FA (P < 0.002), higher ADC (P < 0.006), and fewer (P < 0.005) fibers than younger subjects. Group x region interactions indicated disproportionately lower FA (P = 0.0001) and higher ADC (P < 0.006) in the older than younger group in frontal fiber bundles relative to posterior bundles. As a test of the functional significance of the fiber bundle metrics, the older subjects were administered the Stroop Task, which showed significant correlations between regional fiber bundle integrity and performance. These results validate this quantitative fiber tracking approach and confirm the selective vulnerability of frontal white matter systems to normal aging, likely substrates of age-related declines in cognitive processes dependent on prefrontal circuitry integrity.

Adult↗