Organization of cortical afferent and efferent pathways in the white matter of the rat visual system.

Fibers forming reciprocal connections between the dorsal lateral geniculate nucleus and primary visual cortex run in separate tracts in the white matter. The corticofugal fibers are organized into bundles which project through the coronal plane at an oblique angle. We have examined the organization of corticofugal fiber tracts within the white matter of the rat using cortical slices which encompassed the predicted trajectory of these fiber bundles. Field potentials were evoked in layer VI of visual cortex by focal stimulation of subcortical white matter using microbipolar electrodes. Two major responses were elicited: a short-latency and a longer-latency response. The short-latency response was elicited in the superficial strata of white matter with proximal stimulation sites and was obtained in deeper strata for more distant, lateral sites. The longer-latency response was associated with superficial strata in white matter at both proximal and distant stimulation sites. Based on the electrophysiological properties and the white matter location for eliciting these responses, it is likely that the short-latency response is due to antidromic activation of corticogeniculate fibers, whereas the longer-latency response probably arises from orthodromic activation of geniculocortical fibers. These findings provide an electrophysiological demonstration that cortical afferent and efferent pathways are segregated within the white matter and that they can be selectively activated by focal stimulation. The fact that the fiber bundle model successfully predicted the trajectory of corticofugal fibers provides additional support for this model of white matter organization. A double labeling technique which combined orthograde axonal transport and neuronal degeneration was used to examine the topographic arrangement of corticofugal fibers in the white matter.(ABSTRACT TRUNCATED AT 250 WORDS)     

Extended Broca’s Area in the Functional Connectome of Language in Adults: Combined Cortical and Subcortical Single-Subject Analysis Using fMRI and DTI Tractography

Traditional models of the human language circuitry encompass three cortical areas, Broca’s, Geschwind’s and Wernicke’s, and their connectivity through white matter fascicles. The neural connectivity deep to these cortical areas remains poorly understood, as does the macroscopic functional organization of the cortico-subcortical language circuitry. In an effort to expand current knowledge, we combined functional MRI (fMRI) and diffusion tensor imaging to explore subject-specific structural and functional macroscopic connectivity, focusing on Broca’s area. Fascicles were studied using diffusion tensor imaging fiber tracking seeded from volumes placed manually within the white matter. White matter fascicles and fMRI-derived clusters (antonym-generation task) of positive and negative blood-oxygen-level-dependent (BOLD) signal were co-registered with 3-D renderings of the brain in 12 healthy subjects. Fascicles connecting BOLD-derived clusters were analyzed within specific cortical areas: Broca’s, with the pars triangularis, the pars opercularis, and the pars orbitaris; Geschwind’s and Wernicke’s; the premotor cortex, the dorsal supplementary motor area, the middle temporal gyrus, the dorsal prefrontal cortex and the frontopolar region. We found a functional connectome divisible into three systems—anterior, superior and inferior—around the insula, more complex than previously thought, particularly with respect to a new extended Broca’s area. The extended Broca’s area involves two new fascicles: the operculo-premotor fascicle comprised of well-organized U-shaped fibers that connect the pars opercularis with the premotor region; and (2) the triangulo-orbitaris system comprised of intermingled U-shaped fibers that connect the pars triangularis with the pars orbitaris. The findings enhance our understanding of language function.     

Microstructural organizational patterns in the human corticostriatal system

The axons that project into the striatum are known to segregate according to macroscopic cortical systems; however, the within-region organization of these fibers has yet to be described in humans. We used in vivo fiber tractography, in neurologically healthy adults, to map white matter bundles that originate in different neocortical areas, navigate complex fiber crossings, and project into the striatum. As expected, these fibers were generally segregated according to cortical origin. Within a subset of pathways, a patched pattern of inputs was observed, consistent with previous ex vivo histological studies. In projections from the prefrontal cortex, we detected a topography in which fibers from rostral prefrontal areas projected mostly to rostral parts of the striatum and vice versa for inputs originating in caudal cortical areas. Importantly, within this prefrontal system there was also an asymmetry in the subset of divergent projections, with more fibers projecting in a posterior direction than anterior. This asymmetry of information projecting into the basal ganglia was predicted by previous network-level computational models. A rostral-caudal topography was also present at the local level in otherwise somatotopically organized fibers projecting from the motor cortex. This provides clear evidence that the longitudinal organization of input fields, observed at the macroscopic level across cortical systems, is also found at the microstructural scale at which information is segregated as it enters the human basal ganglia.     

Somatostatin: localization and distribution in the cortex and the subcortical white matter of human brain

Examination of the cortex and the subcortical white matter by use of an immunocytochemical technique--the per oxidase anti-per oxidase method--shows that somatostatin is located in a widespread neuron system with cell bodies localized in both the cortex and the subcortical white matter of the human brain. In the cortex, the somatostatin cell bodies and fibers are found in all layers, but the fibers are especially numerous in layer I located tangentially to the brain surface. The fibers are very long and subdivide into many branches which form a network of pathways in the deeper cortical layers. There are numerous varicosities along the fibers and they come into close contact with other non-immunoreactive neuronal cells. The somatostatin cells located in the white matter are larger than the somatostatin cells in gray matter. They are giant cells with a size ranging from 50 to 120 micrometers. The fibers from these cells are varicose and can be followed both rostrally into the cortical gray matter and caudally in the subcortical white matter. The localization and the morphology of the somatostatin neurons in the cortex and the subcortical white matter indicate that somatostatin may be able to exert sustained influence in various brain areas and thereby modulate integrative and/or specific functions, not only via connection in the gray matter but also by influencing the neuronal circuits passing through the subcortical white matter.     

Localization and organization of geniculocortical and corticofugal fiber tracts within the subcortical white matter

Reciprocal connections are formed between the dorsal lateral geniculate nucleus and the striate cortex in the mammalian visual system. The question of whether fibers of these corticopetal and corticofugal pathways are segregated or intermingled within the white matter is still open. In order to examine the organization of these fiber tracts within the white matter, we have used orthograde axonal transport of radiolabelled proteins and neuronal degeneration following kainic acid lesions in the geniculocortical and corticofugal pathways of the rat. Within the white matter the two pathways reside in different layers and are segregated from one another over a significant portion of their course, geniculocortical fibers lying in the external sagittal stratum and corticofugal fibers lying in the internal sagittal stratum of the white matter. In addition, the corticofugal pathways projecting to subcortical structures appear fasciculated in both the transport and the degeneration studies suggesting that axons of cortical output neurons are organized into fiber bundles. The separation of fibers within the white matter may be of potential use for selectively stimulating afferent and efferent pathways in electrophysiological studies in situ and in cortical slice preparations. In addition, the corticofugal fiber bundles may play an important role in guiding axons therein to appropriate targets during axonogeneis and may carry the output of columnar units within visual cortex.     

Postnatal development of corticospinal postsynaptic action

The corticospinal system has a delayed and prolonged postnatal development. In the cat, lesion, inactivation, or stimulation of the system influence motor output minimally when corticospinal (CS) terminals have an immature topographic pattern but produce robust effects immediately after developing the mature pattern by weeks 6-7. In this study, we directly tested if the delay in expression of cortical motor functions is due to the inability of the corticospinal synapse to activate spinal neurons. We stimulated corticospinal axons in the pyramid and recorded evoked field potentials from the surface of the cervical spinal cord and locally from within the gray matter in anesthetized cats during development and in adults. Pyramidal stimulation in animals between week 4 and maturity evoked an initial corticospinal surface volley followed by a postsynaptic field response. Depth recordings from the superficial dorsal horn to the ventral white matter showed that local pre- and postsynaptic field potentials could be recorded over the full extent of the gray matter in 4- to 5-wk animals but were restricted to the intermediate zone in older animals and adults. Dorsoventral refinement of CS field potentials parallels anatomical refinement of individual CS axon terminals shown in our earlier studies. Our present findings indicate that the developing corticospinal system could influence the excitability of virtually the entire contralateral gray matter before cortical motor functions are expressed. Given the importance of activity-dependent axon terminal refinement, this capacity for activating spinal neurons during early postnatal life could play an important role in development of CS circuit connectivity.     

Subcortical anatomy of the lateral association fascicles of the brain: A review

Precise knowledge of the connectivities of the different white matter bundles is of great value for neuroscience research. Our knowledge of subcortical anatomy has improved exponentially during recent decades owing to the development of magnetic resonance diffusion tensor imaging tractography (DTI). Although DTI tractography has led to important progress in understanding white matter anatomy, the precise trajectory and cortical connections of the subcortical bundles remain poorly determined. The recent literature was extensively reviewed in order to analyze the trajectories and cortical terminations of the lateral association fibers of the brain.The anatomy of the following tracts is reviewed: superior longitudinal fasciculus, middle longitudinal fasciculus, inferior longitudinal fasciculus, inferior fronto‐occipital fasciculus, uncinate fasciculus, frontal aslant tract, and vertical occipital fasciculus. The functional role of a tract can be inferred from its topography within the brain. Knowing the functional roles of the cortical areas connected by a certain bundle, it is possible to develop new insights into the putative functional properties of such connections. Clin. Anat. 563–569, 2014. © 2014 Wiley Periodicals, Inc.     

Quantitative fiber tracking of lateral and interhemispheric white matter systems in normal aging: relations to timed performance

The integrity of white matter, as measured in vivo with diffusion tensor imaging (DTI), is disrupted in normal aging. A current consensus is that in adults advancing age affects anterior brain regions disproportionately more than posterior regions; however, the mainstay of studies supporting this anterior-posterior gradient is based primarily on measures of the corpus callosum. Using our quantitative fiber tracking approach, we assessed fiber tract integrity of samples of major white matter cortical, subcortical, interhemispheric, and cerebellar systems (11 bilateral and 2 callosal) on DTI data collected at 1.5T magnet strength. Participants were 55 men (age 20-78 years) and 65 women (age 28-81 years), deemed healthy and cognitively intact following interview and behavioral testing. Fiber integrity was measured as orientational diffusion coherence (fractional anisotropy, FA) and magnitude of diffusion, which was quantified separately for longitudinal diffusivity (lambdaL), an index of axonal length or number, and transverse diffusivity (lambdaT), an index of myelin integrity. Aging effects were more evident in diffusivity than FA measures. Men and women, examined separately, showed similar age-related increases in longitudinal and transverse diffusivity in fibers of the internal and external capsules bilaterally and the fornix. FA was lower and diffusivity higher in anterior than posterior fibers of regional paired comparisons (genu versus splenium and frontal versus occipital forceps). Diffusivity with older age was generally greater or FA lower in the superior than inferior fiber systems (longitudinal fasciculi, cingulate bundles), with little to no evidence for age-related degradation in pontine or cerebellar systems. The most striking sex difference emerged for the corpus callosum, for which men showed significant decline in FA and increase in longitudinal and transverse diffusivity in the genu but not splenium. By contrast, in women the age effect was present in both callosal regions, albeit modestly more so in the genu than splenium. Functional meaningfulness of these age-related differences was supported by significant correlations between DTI signs of white matter degradation and poorer performance on cognitive or motor tests. This survey of multiple fiber systems throughout the brain revealed a differential pattern of age's effect on regional FA and diffusivity and suggests mechanisms of functional degradation, attributed at least in part to compromised fiber microstructure affecting myelin and axonal morphology.     

Organization of somatic motor inputs from the frontal lobe to the pedunculopontine tegmental nucleus in the macaque monkey

To reveal the somatotopy of the pedunculopontine tegmental nucleus that functions as a brainstem motor center, we examined the distribution patterns of corticotegmental inputs from the somatic motor areas of the frontal lobe in the macaque monkey. Based on the somatotopical map prepared by intracortical microstimulation, injections of the anterograde tracers, biotinylated dextran amine and wheat germ agglutinin-conjugated horseradish peroxidase, were made into the following motor-related areas: the primary motor cortex, the supplementary and presupplementary motor areas, the dorsal and ventral divisions of the premotor cortex, and the frontal eye field. Data obtained from the present experiments were as follows: (i) Corticotegmental inputs from orofacial, forelimb, and hindlimb representations of the primary motor cortex tended to be arranged orderly from medial to lateral in the pedunculopontine tegmental nucleus. However, the distribution areas of these inputs considerably overlapped; (ii) The major input zones from distal representations of the forelimb and hindlimb regions of the primary motor cortex were located medial to those from their proximal representations, although there was a substantial overlap between the distribution areas of distal versus proximal limb inputs; (iii) The main terminal zones from the forelimb regions of the primary motor cortex, the supplementary and presupplementary motor areas, and the dorsal and ventral divisions of the premotor cortex appeared to overlap largely in the mediolaterally middle aspect of the pedunculopontine tegmental nucleus; and (iv) Corticotegmental input from the frontal eye field was scattered over the pedunculopontine tegmental nucleus.Thus, the present results indicate that the pedunculopontine tegmental nucleus is likely to receive partly separate but essentially convergent cortical inputs not only from multiple motor-related areas representing the same body part, but also from multiple regions representing diverse body parts. This suggests that somatotopical representations are intermingled rather than segregated in the pedunculopontine tegmental nucleus.     

Does the left superior longitudinal fascicle subserve language semantics? A brain electrostimulation study

Recent diffusion tensor imaging (DTI) tractography studies indicate that the supramarginal gyrus (SMG) represents a relay between frontal and temporal language sites. Some authors postulate that pathways connecting SMG to the posterior temporal lobe, i.e., the posterior part of the superior longitudinal fascicle (SLF) subserve semantic aspects of language. However, DTI provides only anatomic but not functional data. Therefore, it is impossible to conclude. Interestingly, intra-operative electrical mapping of cortical and subcortical language structures during tumor surgery is recognized as a reliable technique in functional neuroanatomy research. We mapped the underlying white matter of the SMG, especially the SLF, in 11 patients who underwent awake surgery for a glioma involving the left inferior parietal lobule. Using direct electrostimulation, we investigated the exact role of the SLF in language. Our findings indicate that the white matter under the inferior parietal lobule is highly involved in the dorsal phonological system. First, the SMG, connected to the ventral premotor cortex by horizontal fibers of the SLF, subserves articulatory processing, as demonstrated by dysarthria elicited by stimulation. Second, long arcuate fibers, found deeper in the white matter, subserve phonological processing, as supported by phonemic paraphasia induced by electrostimulation. Third, the most important result is that no semantic disturbances were elicited by stimulating the SLF, including its posterior part. Furthermore, no semantic disorders occurred postoperatively. Subcortical brain mapping by direct electrical stimulation does not provide arguments for a possible role of the left SLF in language semantic processing.     

Motor cortical organization in an adult with hemimegalencephaly and late onset epilepsy

Hemimegalencephaly is a rare brain malformation whose physiology is largely obscure. In a single patient, we studied motor cortex using several transcranial magnetic stimulation variables testing cortical excitability, and mapping motor area. The megalencephalic hemisphere showed an enlargement of cortical motor map with abnormal axonal orientation and an excess spread of corticospinal excitation, associated with multiple defects of cortical inhibition. TMS gave new information on the anatomic/functional features and epileptogenesis in this complex and physiologically obscure syndrome.     

Reorganization of remote cortical regions after ischemic brain injury: a potential substrate for stroke recovery

Although recent neurological research has shed light on the brain's mechanisms of self-repair after stroke, the role that intact tissue plays in recovery is still obscure. To explore these mechanisms further, we used microelectrode stimulation techniques to examine functional remodeling in cerebral cortex after an ischemic infarct in the hand representation of primary motor cortex in five adult squirrel monkeys. Hand preference and the motor skill of both hands were assessed periodically on a pellet retrieval task for 3 mo postinfarct. Initial postinfarct motor impairment of the contralateral hand was evident in each animal, followed by a gradual improvement in performance over 1-3 mo. Intracortical microstimulation mapping at 12 wk after infarct revealed substantial enlargements of the hand representation in a remote cortical area, the ventral premotor cortex. Increases ranged from 7.2 to 53.8% relative to the preinfarct ventral premotor hand area, with a mean increase of 36.0 +/- 20.8%. This enlargement was proportional to the amount of hand representation destroyed in primary motor cortex. That is, greater sparing of the M1 hand area resulted in less expansion of the ventral premotor cortex hand area. These results suggest that neurophysiologic reorganization of remote cortical areas occurs in response to cortical injury and that the greater the damage to reciprocal intracortical pathways, the greater the plasticity in intact areas. Reorganization in intact tissue may provide a neural substrate for adaptive motor behavior and play a critical role in postinjury recovery of function.     

Cells of origin of crossed and uncrossed corticospinal fibers in the cat

Summary The cortical distribution of the cells of origin of the dorsolateral and the ventral corticospinal tracts was studied in cat. This was done by making subtotal spinal transections, which in different experiments spared different portions of one ventral or one lateral funiculus at C5–C7. One week later horseradish peroxidase (HRP) injections were made one segment caudal to the lesion and the cortical distribution of the HRP labeled neurons was studied.Thus, it was found that the dorsolateral corticospinal tract at C5–C7 is composed of crossed and uncrossed fibers in a ratio of about 10 1, while the ventral corticospinal tract, which contains much fewer cortical fibers, is composed of crossed and uncrossed fibers in a ratio of approximately 1 1. Further, the primary motor cortex (area 4) was found to contribute fibers to both the crossed and the uncrossed dorsolateral corticospinal tract as well as to both the crossed and the uncrossed ventral corticospinal tract. The primary somatosensory cortex (area 3a, 3b, 1–2, 5a, 5b) as well as the secondary somatosensory cortex (area 2 pre-insularis), on the other hand, were found to contribute fibers mainly to the crossed dorsolateral tract. Area 4 was found to display a further organization, such that it contains a medial and a lateral part, both of which contribute mainly fibers to the crossed dorsolateral tract, while the remainder of area 4 contributes fibers to the crossed and uncrossed dorsolateral as well as to the crossed and uncrossed ventral tracts.This study was in part supported by grant 13.46.15 of the FUNGO/ZWO (Dutch Organization for Fundamental Research in Medicine) and grant C.R.L. 79.4.337.6.INT. of the INSERM (Institut National de la Santé et de la Recherche Médicale)     

Training in a ballistic task but not a visuomotor task increases responses to stimulation of human corticospinal axons

Short periods of training in motor tasks can increase motor cortical excitability. This study investigated whether changes also occur at a subcortical level. Subjects trained in ballistic finger abduction or visuomotor tracking. The right index finger rotated around the metacarpophalangeal (MCP) joint in a splint. Surface EMG was recorded from the first dorsal interosseous. Transcranial magnetic stimulation over the back of the head (double-cone coil) elicited cervicomedullary motor evoked potentials (CMEPs) by stimulation of corticospinal axons. Responses were recorded from the relaxed muscle before, between, and after two sets of training. In study 1 (n = 7), training comprised two sets of 150 maximal finger abductions. Feedback of acceleration was provided. With training, acceleration increased significantly. CMEPs increased to 248 ± 152% (± SD) of baseline immediately after training (P = 0.007) but returned to control level (155 ± 141%) 10 min later. In study 2 (n = 7), subjects matched MCP joint angle to a target path on a computer screen. After ～30 min of training, tracking improved as shown by increased correlation between joint angle and the target pathway, reduced time lag, and reduced EMG(rms). However, CMEPs remained unchanged. These results show that transmission through the corticospinal pathway at a spinal level increased after repeated ballistic movements but not after training in a visuomotor task. Thus, changes at a spinal level may contribute to improved performance in some motor tasks.     

Cerebello-cerebral connectivity deficits in Friedreich ataxia

Brain pathology in Friedreich ataxia is characterized by progressive degeneration of nervous tissue in the brainstem, cerebellum and cerebellar peduncles. Evidence of cerebral involvement is however equivocal. This brain imaging study investigates cerebello-cerebral white matter connectivity in Friedreich ataxia with diffusion MRI and tractography performed in 13 individuals homozygous for a GAA expansion in intron one of the frataxin gene and 14 age- and gender-matched control participants. New evidence is presented for disrupted cerebello-cerebral connectivity in the disease, leading to secondary effects in distant cortical and subcortical regions. Remote regions affected by primary cerebellar and brainstem pathology include the supplementary motor area, cingulate cortex, frontal cortices, putamen and other subcortical nuclei. The connectivity disruptions identified provide an explanation for some of the non-ataxic symptoms observed in the disease and support the notion of reverse cerebellar diaschisis. This is the first study to comprehensively map white matter connectivity disruptions in Friedreich ataxia using tractography, connectomic techniques and super-resolution track density imaging.     

Neural basis for the processes that underlie visually guided and internally guided force control in humans

Despite an intricate understanding of the neural mechanisms underlying visual and motor systems, it is not completely understood in which brain regions humans transfer visual information into motor commands. Furthermore, in the absence of visual information, the retrieval process for motor memory information remains unclear. We report an investigation where visuomotor and motor memory processes were separated from only visual and only motor activation. Subjects produced precision grip force during a functional MRI (fMRI) study that included four conditions: rest, grip force with visual feedback, grip force without visual feedback, and visual feedback only. Statistical and subtractive logic analyses segregated the functional process maps. There were three important observations. First, along with the well-established parietal and premotor cortical network, the anterior prefrontal cortex, putamen, ventral thalamus, lateral cerebellum, intermediate cerebellum, and the dentate nucleus were directly involved in the visuomotor transformation process. This activation occurred despite controlling for the visual input and motor output. Second, a detailed topographic orientation of visuomotor to motor/sensory activity was mapped for the premotor cortex, parietal cortex, and the cerebellum. Third, the retrieval of motor memory information was isolated in the dorsolateral prefrontal cortex, ventral prefrontal cortex, and anterior cingulate. The motor memory process did not extend to the supplementary motor area (SMA) and the basal ganglia. These findings provide evidence in humans for a model where a distributed network extends over cortical and subcortical regions to control the visuomotor transformation process used during visually guided tasks. In contrast, a localized network in the prefrontal cortex retrieves force output from memory during internally guided actions.     

Estimation of white matter connectivity based on a three-dimensional directional diffusion function in diffusion tensor MRI

Diffusion tensor (DT) magnetic resonance imaging (MRI) provides the directional information of local neuronal fibers, and has been used to estimate the neuroanatomical connectivity in the cerebral white matter. Several methods for white matter tractography have been developed based on DT-MRI. However, it has been difficult to estimate the white matter tract pathways in the fiber crossing and branching region because of the ambiguity of the principal eigenvector and/or low anisotropy due to the partial volume effect. In this paper, we proposed a new method for white matter tractography, which permits fiber tract branching and passing through crossing regions. Our tractography method is based on a three-dimensional (3D) directional diffusion function (DDF), which was given by a 3D anisotropic Gaussian function defined by normalized three eigenvalues and their corresponding eigenvectors of DT. The DDF was used for generation of a 3D directional diffusion field and for determination of the connectivity between the voxels in fiber tracking. To extract the white matter tract region, DDF-based tractography (DDFT) method used the directional diffusion field instead of a threshold fractional anisotropy map, which has been used in the conventional methods, so that low anisotropy voxels in the branching and crossing regions may be included. We applied the DDFT method and two conventional tractography methods (a streamline technique and a tensorline algorithm) to DT-MRI data of five normal subjects for visualizing the pyramidal tract. Our method visualized the pathways connected to a large portion of the primary motor cortex, including foot, hand and face motor areas, passing through the crossing regions with other white matter tracts in all subjects, whereas the conventional methods showed only a small portion of the pyramidal tract. The pyramidal tract pathways estimated by our method were consistent with the neuroanatomical knowledge. In conclusion, the DDFT method may be useful in assisting neuroradiologists in estimating the white matter tracts.     

A light and electron microscopic study of the iron transporter protein DMT-1 in the monkey cerebral neocortex and hippocampus

We have studied by immunocytochemistry, the distribution of DMT-1, a cellular iron transporter responsible for transport of metal irons from the plasma membrane to endosomes, in the normal monkey cerebral neocortex and hippocampus. Light to moderate DMT-1 staining was observed in glial cell bodies in the neocortex, the subcortical white matter, and the hippocampus. Despite light labeling of cell bodies, glial end feet around cortical and subcortical blood vessels were heavily labeled. In the neocortex, the glial cell bodies displayed the morphological features of protoplasmic astrocytes. Labeled glial cells in the subcortical white matter contained dense bundles of glial filaments and were identified as fibrous astrocytes. The observation that DMT-1 was present on astrocytic endfeet suggests that these cells are involved in uptake of iron from endothelial cells. It is possible that the iron could then be redistributed into the extracellular space in the brain parenchyma.     

White matter damage precedes that in gray matter despite similar magnetic resonance imaging changes following cerebral hypoxia-ischemia in neonatal rats

We hypothesized that the cerebral injury produced by hypoxia-ischemia (HI) in neonatal rats would differ in white compared with gray matter as detected histologically or with magnetic resonance (MR) imaging methods. Maps of T₂ and the apparent diffusion coefficient (ADC) of water were acquired in 1-week-old rats at times prior to cerebral HI (right carotid artery occlusion plus 1.5 h of hypoxia), within the last 5–10 min of HI, and 1 h or 24 h after HI. Near the end of HI, ADC decreased and T₂ increased in both cortical gray and subcortical white matter within the cingulum of the HI hemisphere. One hour after HI, ADC partially recovered, but T₂ remained increased and then increased further by 24 h post-HI. In contrast to the similar MR responses in white and gray matter, histological evidence for irreversible cell damage occurred in white matter earlier than in gray matter within the HI hemisphere. At 1 h post-HI, rarefied or disrupted nerve fibers and an increase in TUNEL-positive cells were observed within white matter in the cingulum, whereas neurons within the cortical gray matter appeared normal. By 24 h post-HI, damage was apparent in both white and gray matter. Thus, MR imaging detected acute tissue edema following cerebral HI in both gray and white matter but did not distinguish between the early irreversible tissue injury detected histologically in white but not gray matter in this rather severe model of neonatal encephalopathy.     

White matter integrity of motor connections related to training gains in healthy aging

Impaired motor skill acquisition is a feature of older age. Acquisition of new motor skills requires the interplay between different cortical motor areas. Using diffusion tensor imaging we reconstructed cortico-cortical connections between the primary motor cortex (M1) and secondary motor areas in 11 older and 11 young participants who took part in a motor skill acquisition paradigm with the nondominant left hand. Examining the extent to which tract-related integrity correlated with training gains we found that white matter integrity of fibers connecting contralateral M1 with both contralateral (r = 0.85) and ipsilateral supplementary motor areas (r = 0.92) were positively associated in old participants. Also, fibers connecting contralateral M1 with ipsilateral dorsal premotor (r = 0.82) and fibers connecting ipsilateral dorsal premotor and supplementary motor area (r = 0.88) were positively related to skill acquisition (all p < 0.05). A similar structure-behavior relationship was not present in the young control subjects suggesting a critical role of brain structural integrity for motor learning in healthy aging.