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The basal ganglia-circa 1982. A review and commentary.

Our review has shown that recent studies with the new anterograde and retrograde axon transport methods have confirmed and extended our knowledge of the projection of the basal ganglia and clarified their sites of origin. They have thrown new light on certain topographic connectional relationships and revealed several new reciprocal connections between constituent nuclei of the basal ganglia. Similarly, attention has been drawn to the fact that there have also been many new histochemical techniques introduced in recent years that are now providing regional biochemical overlays for connectional maps of the central nervous system, especially regions in, or interconnecting with, the basal ganglia. However, although these new morphological biochemical maps are very complex and technically highly advanced, our understanding of the function controlled by the basal ganglia still remains primitive. The reader who is interested in some new ideas of the functional aspects of the basal ganglia is directed to Nauta's [88] proposed conceptual reorganization of the basal ganglia telencephalon and to Marsden's [72] more clinically orientated appraisal of the unsolved mysteries of the basal ganglia participation in the control of movement.

Afferent Pathways↗

Auditory connections and neurochemistry of the sagulum.

We studied the cytoarchitecture, neurochemical organization, and connections of the sagulum. The goal was to clarify its role in midbrain, lateral tegmental, and thalamic auditory processing. On cytoarchitectonic grounds, ventrolateral (parvocellular) and dorsomedial (magnocellular) subdivisions were recognized. The patterns of immunostaining for gamma-aminobutyric acid (GABA) and glycine were distinct. Approximately 5-10% of the neurons were GABAergic, and more than one type was identified; GABAergic axon terminals were abundant in number and varied in form. Glycinergic neurons were much rarer, < 1% of the population, and glycinergic axon terminals were correspondingly sparse. Wheat germ agglutinin conjugated to horseradish peroxidase was used for purposes of connectional mapping, and biotinylated dextran amines revealed the structure of corticosagular axons. All nine cortical areas injected project to the ipsilateral sagulum. Five (areas AI, AII, SF, EPD, and Te) had heavier projections than the others. Areas AI and AII projected throughout the rostrocaudal sagulum. Labeling from AI was moderate in density and concentrated in the central sagulum, whereas the input from AII was heavier and ended more laterally. Suprasylvian fringe input was light, especially caudally, and was chiefly in the central sagulum. The projection from the dorsal region of the posterior ectosylvian gyrus was comparatively stronger and was in the dorsolateral sagulum. Finally, the temporal cortex sent axons to the most lateral sagulum, spanning the dorsoventral extent, whereas insular cortex axons ended diffusely in the dorsolateral sagulum. Corticofugal axons ranged from fine boutons en passant to larger globular terminals. The sagulum may represent the earliest significant opportunity in the ascending auditory pathway for corticofugal modulation. The most extensive input arises from the polymodal association areas. The sagulum then projects divergently to the dorsal cortex of the inferior colliculus and the dorsal division of the medial geniculate body. The projection from the dorsal division of the auditory thalamus to nonprimary auditory cortex completes this circuit between the forebrain and the midbrain and represents a nexus in the ascending and descending auditory systems. Such circuits could play a critical role in auditory-motor adjustments to sound.

Anatomy, Artistic↗

Recognition of abnormal connections of coronary arteries with the use of Doppler color flow mapping.

Anomalous connection of a coronary artery to a ventricle or pulmonary artery causes shunting of blood from the coronary circuit and may produce myocardial ischemia. Such a coronary anomaly may occur in isolation or with other defects. Doppler color flow mapping and two-dimensional echocardiography were used to diagnose anomalous coronary connections in 13 patients, 1 day to 7 years of age, over a 1 year period. The diagnoses were anomalous origin of the left coronary artery from the pulmonary trunk in five patients, a coronary artery to left ventricle fistula or coronary artery to pulmonary artery fistula in four patients with other complex defects, right ventricular sinusoids in two patients with pulmonary atresia and intact ventricular septum and an isolated coronary artery fistula in two patients. In all cases, the abnormal coronary connection was recognized on the basis of an abnormal, continuous or to and fro flow pattern in the fistula and its connections as demonstrated by scanning in multiple views with Doppler color flow mapping. The low spatial resolution of Doppler color flow mapping limits the anatomic detail available; nonetheless, it is a significant advance in the noninvasive diagnosis of abnormal coronary connections.

Arterio-Arterial Fistula↗

Two-dimensional population map of cortical connections in the human internal capsule.

PURPOSE: To exploit diffusion imaging tractography to produce a two-dimensional (xy) probabilistic population map of the cortical connections within the human internal capsule (IC). MATERIALS AND METHODS: Diffusion tensor imaging (DTI) was carried out on 11 healthy volunteers. We parceled an axial section of the IC according to its connections to the prefrontal, premotor, primary motor, primary somatosensory, posterior parietal, and occipital cortices using our locally developed probabilistic algorithm. RESULTS: A consistent topographical organization was generated that was consistent with our anatomical knowledge of the IC. In addition, our study shows that in humans the anterior half of the IC is occupied by the prefrontal cortex. CONCLUSION: This map may be of clinical use for correlating neurological deficit with hemispheric lesions, particularly those that affect sensorimotor function.

Adult↗

Immature cortex lesions alter retinotopic maps and interhemispheric connections.

Unilateral lesions of the occipital visual areas performed on postnatal day 5 (P5) in the ferret are not compensated by the appearance, in the lesioned hemisphere, of visual responses at ectopic locations. Instead, when parts of the visual areas are spared, they show abnormal retinotopic organizations; furthermore, callosal connections are abnormally distributed in relation to the retinotopic maps. Lesions that completely eliminate the visual areas including the posterior parietal cortex cause the appearance of abnormal callosal connections from the primary somatosensory cortex on the lesion side to the contralateral, intact, posterior parietal cortex. The occipital visual areas (17, 18, 19, and 21) of the intact hemisphere show a normal retinotopy but lose callosal connections in territories homotopic to the lesions. These findings clarify the nature and limits of structural developmental plasticity in the visual cortex. Early in life, certain regions of cortex have been irreversibly allocated to the visual areas, but two properties defining the areas, that is, retinotopy and connections, remain modifiable. The findings might be relevant for understanding the consequences of early-onset visual cortical lesions in humans.

Agenesis of Corpus Callosum↗

Functional mapping of horizontal connections in developing ferret visual cortex: experiments and modeling.

In cat striate cortex, patchy horizontal axonal projections link columns of similar orientation specificity. To assess the physiological correlates of such clustered projections, a new multisite stimulation technique was used to functionally map the pattern of horizontal synaptic inputs onto single layer 2/3 cells within tangential slices of developing ferret visual cortex. Twenty-four separate sets of horizontal fibers were stimulated within a 1200 microns strip of cortex, while evoked synaptic responses were recorded using whole-cell patch methods. For most cells, input maps demonstrated the presence of clustered horizontal connections in which multiple strong and weak synaptic responses were alternately evoked across the stimulated cortical region. Recordings from up to nine cells in a single slice revealed that patterns of synaptic input were closely correlated for cells in close proximity, and that this correlation decreased with distance, with no correlation at distances greater than 500 microns. To determine whether these physiological results were consistent with the known anatomical linkage of iso-orientation columns by clustered horizontal connections, mathematical analysis and computer simulations were performed upon orientation tuning maps obtained from optical imaging of activity-dependent intrinsic signals in mature ferret visual cortex. Optical imaging revealed an organization of iso-orientation domains consisting of broad regions of cortex across which orientation preference smoothly varied, together with "orientation centers" around which orientation preference was arranged in a pinwheel manner. The distribution of synaptic connections between different cortical sites was simulated by a model of functionally linked iso- orientation columns. Simulated synaptic input maps, generated by the same stimulation and recording arrangements used in our experimental protocol, accurately reproduced the observed patterns of clustered inputs onto experimentally recorded cells. These results indicate that even at the time of eye opening, prior to extensive visual experience, most cells receive patterns of synaptic inputs consistent with a clustered organization of horizontal connections that functionally link iso-orientation columns.

Animals↗

Electron microscopy of experimental axonal degeneration in photochemically modified Golgi preparations: a procedure for precise mapping of nervous connections.

A new version is presented of a procedure for bleaching (deimpregnating) silver chromate Golgi preparations through ultraviolet (UV) light irradiation followed by thiosulphate treatment, leaving only scattered particles of metallic silver. This version gives a better ultrastructure of the tissue than obtained before. Moreover, the results of studying a specific connection in such material are reported. The perforant path, connecting the entorhinal area with the hippocampus and fascia dentata, was transected in the rat and after a 2-day survival the brain was subjected to Golgi impregnation followed by the deimpregnation procedure. Blocks of tissue containing impregnated fascia dentata granule cell dendrites were selected for electron microscopy. Postsynaptic thickenings associated with degenerated boutons could be discerned within the deimpregnated dendrites, proving that the entorhino-dentate fibres end on the dendrites of the granule cells (smooth surfaces as well as spines) and that they end at asymmetric junctions (of Gray's type 1). While this conclusion was as expected from previous experimental studies carried out with different methods it is thought that the same strategy for cell-to-cell mapping of nervous connections may be used also in other parts of the central nervous system.

Animals↗

An explanation of contextual modulation by short-range isotropic connections and orientation map geometry in the primary visual cortex.

Recent experimental studies on the primary visual cortex have revealed complicated nonclassical neuronal activities. Contextual modulation on orientation-contrast is one typical example of nonclassical neuronal behavior. This modulation by surrounding stimuli in a nonclassical receptive field is mainly thought to be mediated by short- and long-range horizontal connections within the primary visual cortex. Short-range connections are circularly symmetrical and relatively independent of orientation preferences, while long-range connections are patchy, asymmetrical, and orientation specific. Although this modulation can be explained by long-range specific connections qualitatively, recent studies suggest that long-range connections alone may be insufficient with respect to the balance between two types of connections. Here, in order to clarify the role of short-range connections in the process of contextual modulation, we propose a model of the primary visual cortex with isotropic short-range connections and a geometric orientation map. Computational simulations using the model have demonstrated that contextual modulation can be explained by short-range connections alone. This is due to the interaction between the spatial periodicity of orientation domains and the excitatory-inhibitory regions arising from the propagation of activities.

Action Potentials↗

Probabilistic Monte Carlo based mapping of cerebral connections utilising whole-brain crossing fibre information.

A methodology is presented for estimation of a probability density function of cerebral fibre orientations when one or two fibres are present in a voxel. All data are acquired on a clinical MR scanner, using widely available acquisition techniques. The method models measurements of water diffusion in a single fibre by a Gaussian density function and in multiple fibres by a mixture of Gaussian densities. The effects of noise on complex MR diffusion weighted data are explicitly simluated and parameterised. This information is used for standard and Monte Carlo streamline methods. Deterministic and probabilistic maps of anatomical voxel scale connectivity between brain regions are generated.

Algorithms↗

Elimination and strengthening of glycinergic/GABAergic connections during tonotopic map formation.

Synapse elimination and strengthening are central mechanisms for the developmental organization of excitatory neuronal networks. Little is known, however, about whether these processes are also involved in establishing precise inhibitory circuits. We examined the development of functional connectivity before hearing onset in rats in the tonotopically organized, glycinergic pathway from the medial nucleus of the trapezoid body (MNTB) to the lateral superior olive (LSO), which is part of the mammalian sound localization system. We found that LSO neurons became functionally disconnected from approximately 75% of their initial inputs, resulting in a two-fold sharpening of functional topography. This was accompanied by a 12-fold increase in the synaptic conductance generated by maintained individual inputs. Functional elimination of MNTB-LSO synapses was restricted to the period when these glycinergic/GABAergic synapses are excitatory. These results provide new insights into the mechanisms by which precisely organized inhibitory circuits are established during development.

Aging↗

Analysis of functional magnetic resonance imaging data using self-organizing mapping with spatial connectivity.

Commonly used methods in analyzing functional magnetic resonance imaging (fMRI) data, such as the Student's t-test and cross-correlation analysis, are model-based approaches. Although these methods are easy to implement and are effective in analyzing data obtained with simple paradigms, they are not applicable in situations in which patterns of neuronal response are complicated and when fMRI response is unknown. In this work, Kohonen's self-organizing mapping (SOM), which is a model-free approach, is adapted for analyzing fMRI data. Because spatial connectivity is an important function in the identification of activation sites in functional brain imaging, it is incorporated into the SOM algorithm. Receiver operating characteristic analysis on simulated data shows that the new algorithm achieves measurable improvement over the standard algorithm. The applicability of the new algorithm is demonstrated on experimental data.

Algorithms↗

Principal component analysis and the scaled subprofile model compared to intersubject averaging and statistical parametric mapping: I. "Functional connectivity" of the human motor system studied with [15O]water PET.

Using [15O]water PET and a previously well studied motor activation task, repetitive finger-to-thumb opposition, we compared the spatial activation patterns produced by (1) global normalization and intersubject averaging of paired-image subtractions, (2) the mean differences of ANCOVA-adjusted voxels in Statistical Parametric Mapping, (3) ANCOVA-adjusted voxels followed by principal component analysis (PCA), (4) ANCOVA-adjustment of mean image volumes (mean over subjects at each time point) followed by F-masking and PCA, and (5) PCA with Scaled Subprofile Model pre- and postprocessing. All data analysis techniques identified large positive focal activations in the contralateral sensorimotor cortex and ipsilateral cerebellar cortex, with varying levels of activation in other parts of the motor system, e.g., supplementary motor area, thalamus, putamen; techniques 1-4 also produced extensive negative areas. The activation signal of interest constitutes a very small fraction of the total nonrandom signal in the original dataset, and the exact choice of data preprocessing steps together with a particular analysis procedure have a significant impact on the identification and relative levels of activated regions. The challenge for the future is to identify those preprocessing algorithms and data analysis models that reproducibly optimize the identification and quantification of higher-order sensorimotor and cognitive responses.

Adult↗

Organization of frontoparietal cortex in the tree shrew (Tupaia belangeri). I. Architecture, microelectrode maps, and corticospinal connections.

Despite extensive investigation of the motor cortex of primates, little is known about the organization of motor cortex in tree shrews, one of their closest living relatives. We investigated the organization of frontoparietal cortex in Belanger's tree shrews (Tupaia belangeri) by using intracortical microstimulation (ICMS), corticospinal tracing, and detailed histological analysis. The results provide evidence for the subdivision of tree shrew frontoparietal cortex into seven distinct areas (five are newly identified), including two motor fields (M1 and M2) and five somatosensory fields (3a, 3b, S2, PV, and SC). The types of movements evoked in M1 and M2 were similar, but M2 required higher currents to elicit movements and had few connections to the cervical spinal cord and distinctive cyto- and immunoarchitecture. The borders between M1 and the anterior somatosensory regions (3a and 3b) were identified primarily from histological analysis, because thresholds were similar between these regions, and differences in corticospinal neuron distribution were subtle. The caudal (SC) and lateral (S2 and PV) somatosensory fields were identified based on differences in architecture and distribution of corticospinal neurons. Myelin-dense modules were identified in lateral cortex, in the expected location of the oral, forelimb, and hindlimb representations of S2, and possibly PV. Evidence for a complex primate-like array of motor fields is lacking in tree shrews, but their motor cortex shares a number of basic features with that of primates, which are not found in more distantly related species, such as rats.

Animals↗

Anisotropic reentry in a perfused 2-dimensional layer of rabbit ventricular myocardium.

BACKGROUND: Anisotropy creates nonuniformity in electrical propagation and may contribute to the occurrence of unidirectional conduction block and reentry. We describe the characteristics of reentrant tachycardia in a 2D layer of anisotropic ventricular myocardium. METHODS AND RESULTS: A Langendorff-perfused epicardial sheet (1.0+/-0.4 mm, n=35) was created by freezing the intramural layers of the rabbit left ventricle. Epicardial activation maps were constructed by use of different high-resolution mapping arrays connected to a mapping system. In 5 experiments, monophasic action potentials were recorded. In the intact left ventricle, no arrhythmias except VF could be induced. After freezing, programmed electrical stimulation or rapid pacing led to the induction of sustained VT (cycle length 130+/-11 ms). VT was caused by reentry around a functional line of block oriented parallel to the epicardial fiber direction. Action potential recordings demonstrated that the central line of block was kept refractory by electrotonic currents generated by the depolarization waves propagating at either side of the line of block. At the pivot points of the line of block, the pronounced curvature of the turning wave and abrupt loading changes created an excitable gap of 30 ms in the reentrant pathway. CONCLUSIONS: In uniform anisotropic myocardium, reentry around a functional Z-shaped line of block may occur. The core of the circuit is kept refractory by electrotonic currents. The pronounced wave-front curvature and abrupt loading changes at the pivot points cause local conduction delay and create a small excitable gap.

Action Potentials↗

Radial correlation contrast--a functional connectivity MRI contrast to map changes in local neuronal communication.

A functional connectivity MRI method that groups neighboring voxels in relation to their degree of temporal cross-correlation between their time courses is presented. This grouping generates a vector field, which is assumed to provide insights into the local organization of neuronal activity. Application with high spatial resolution fMRI rat data subjected to electric forepaw sensory stimulation (156 . 156 . 1000 micron1) shows a significant localized increase of the vector field amplitude in cortical layers 4 and 2/3 of the primary sensory cortex and in layer 2/3 of the primary motor cortex, suggesting a strong correlation with local neuronal communication. Vector field phases exhibit a transition with neuronal activation from random-like orientations during rest to clusters of common orientations. Cluster size is shown to be weakly dependent on the radii of the vector field calculation, and shuffling voxel position within clusters generates a random-like vector orientation instead. This suggests that changes in vector orientations upon activation represent changes in the internal correlation between voxels that is interpreted as a change in the internal neuronal communication.

Animals↗