Ralf A. W. Galuske

Hemispheric asymmetries in cerebral cortical networks

Since the middle of the 19th century it has been recognized that several higher cognitive functions, including language, are lateralized in cerebral cortex. Neuropsychological studies on patients with brain lesions and rapid developments in brain imaging techniques have provided us with an increasing body of data on the functional aspects of language lateralization, but little is known about the substrate on which these specializations are realized. Much attention has been focused on the gross size and shape of cortical regions involved, but recent findings indicate that the columnar and connectional structure within auditory and language cortex in the left hemisphere are distinct from those in homotopic regions in the right hemisphere. These findings concern parameters that are closely linked to the processing architecture within the respective regions. Thus, the comparison of these microanatomical specializations with their respective functional counterparts provides important insights into the functional role of cerebral cortical organization and its consequences for processing of cortical information in the implementation of complex cognitive functions.

Gap junctions among dendrites of cortical GABAergic neurons establish a dense and widespread intercolumnar network

Gap junctions are common between cortical GABAergic interneurons but little is known about their quantitative distribution along dendritic profiles. Here, we provide direct morphological evidence that parvalbumin-containing GABAergic neurons in layer 2/3 of the cat visual cortex form dense and far-ranging networks through dendritic gap junctions. Gap junction-coupled networks of parvalbumin neurons were visualized using connexin36 immunohistochemistry and confocal laser-scanning microscopy (CLSM). The direct correspondence of connexin36-immunopositve puncta and gap junctions was confirmed by examining the same structures in both CLSM and electron microscopy. Single parvalbumin neurons with large somata (≥200 μm2) formed 60.3 ± 12.2 (mean ± SD) gap junctions with other cells whereby these contacts were not restricted to proximal dendrites but occurred at distances of up to 380 μm from the soma. In a Sholl analysis of large-type parvalbumin neurons, 21.9 ± 7.9 gap junctions were within 50 μm of the soma, 21.7 ± 7.6 gap junctions in a segment between 50 and 100 μm, 11.2 ± 4.7 junctions between 100 and 150 μm, and 5.6 ± 3.6 junctions were in more distal segments. Serially interconnected neurons could be traced laterally in a boundless manner through multiple gap junctions. Comparison to the orientation-preference columns revealed that parvalbumin-immunoreactive cells distribute randomly whereby their large dendritic fields overlap considerably and cover different orientation columns. It is proposed that this dense and homogeneous electrical coupling of interneurons supports the precise synchronization of neuronal populations with differing feature preferences thereby providing a temporal frame for the generation of distributed representations.

Evolution amplified processing with temporally dispersed slow neuronal connectivity in primates

The corpus callosum (CC) provides the main route of communication between the 2 hemispheres of the brain. In monkeys, chimpanzees, and humans, callosal axons of distinct size interconnect functionally different cortical areas. Thinner axons in the genu and in the posterior body of the CC interconnect the prefrontal and parietal areas, respectively, and thicker axons in the midbody and in the splenium interconnect primary motor, somatosensory, and visual areas. At all locations, axon diameter, and hence its conduction velocity, increases slightly in the chimpanzee compared with the macaque because of an increased number of large axons but not between the chimpanzee and man. This, together with the longer connections in larger brains, doubles the expected conduction delays between the hemispheres, from macaque to man, and amplifies their range about 3-fold. These changes can have several consequences for cortical dynamics, particularly on the cycle of interhemispheric oscillators.

Local active information storage as a tool to understand distributed neural information processing.

Every act of information processing can in principle be decomposed into the component operations of information storage, transfer, and modification. Yet, while this is easily done for todays digital computers, the application of these concepts to neural information processing was hampered by the lack of proper mathematical definitions of these operations on information. Recently, definitions were given for the dynamics of these information processing operations on a local scale in space and time in a distributed system, and the specific concept of local active information storage was successfully applied to the analysis and optimization of artificial neural systems. However, no attempt to measure the space-time dynamics of local active information storage in neural data has been made to date. Here we measure local active information storage on a local scale in time and space in voltage sensitive dye imaging data from area 18 of the cat. We show that storage reflects neural properties such as stimulus preferences and surprise upon unexpected stimulus change, and in area 18 reflects the abstract concept of an ongoing stimulus despite the locally random nature of this stimulus. We suggest that LAIS will be a useful quantity to test theories of cortical function, such as predictive coding.

Brain‐derived Neurotrophic Factor Reverses Experience‐dependent Synaptic Modifications in Kitten Visual Cortex

During a critical period of early postnatal development the functional architecture of the visual cortex is shaped by experience‐dependent circuit selection following a Hebbian mechanism. One consequence is that monocular deprivation (MD) leads to competitive repression of the input from the deprived eye. Recently it has been proposed that this process might involve activity‐dependent competition for neurotrophic substances because the synthesis of brain‐derived neurotrophic factor (BDNF) is regulated by visual input. Here we investigate the effects of intracortical infusion of BDNF and nerve growth factor (NGF) on MD effects in the visual cortex. Neuronal responses were monitored with optical and single‐unit recording techniques in the visual cortex of kittens that had been infused intracortically either with BDNF, NGF or cytochrome C while subjected to MD for 1 week during the peak of the critical period. NGF or cytochrome C had no effect on the consequences of MD. After BDNF treatment, by contrast, ocular dominance (OD) shifted towards the deprived eye in a zone extending 2.5–3.5 mm from the infusion cannula, and neurons lost their orientation selectivity. At intermediate distances both eyes activated the cortex equally well and responses were again tuned for orientation; at still larger distances OD was shifted towards the normal eye. Thus, BDNF antagonizes the functional effects of MD and at high concentrations causes paradoxical disconnection of non‐deprived afferents and a loss of orientation selectivity.

The role of feedback in shaping neural representations in cat visual cortex

In the primary visual cortex, neurons with similar response preferences are grouped into domains forming continuous maps of stimulus orientation and direction of movement. These properties are widely believed to result from the combination of ascending and lateral interactions in the visual system. We have tested this view by examining the influence of deactivating feedback signals descending from the visuoparietal cortex on the emergence of these response properties and representations in cat area 18. We thermally deactivated the dominant motion-processing region of the visuoparietal cortex and used optical and electrophysiological methods to assay neural activity evoked in area 18 by stimulation with moving gratings and fields of coherently moving randomly distributed dots. Feedback deactivation decreased signal strength in both orientation and direction maps and virtually abolished the global layout of direction maps, whereas the basic structure of the orientation maps was preserved. These findings could be accounted for by a selective silencing of highly direction-selective neurons and by the redirection of preferences of less selective neurons. Our data suggest that signals fed back from the visuoparietal cortex strongly contribute to the emergence of direction selectivity in early visual areas. Thus we propose that higher cortical areas have significant influence over fundamental neuronal properties as they emerge in lower areas.

Histological Validation of DW-MRI Tractography in Human Postmortem Tissue

Despite several previous attempts, histological validation of diffusion-weighted magnetic resonance imaging (DW-MRI)-based tractography as true axonal fiber pathways remains difficult. In the present study, we establish a method to compare histological and tractography data precisely enough for statements on the level of single tractography pathways. To this end, we used carbocyanine dyes to trace connections in human postmortem tissue and aligned them to high-resolution DW-MRI of the same tissue processed within the diffusion tensor imaging (DTI) formalism. We provide robust definitions of sensitivity (true positives) and specificity (true negatives) for DTI tractography and characterize tractography paths in terms of receiver operating characteristics. With sensitivity and specificity rates of approximately 80%, we could show a clear correspondence between histological and inferred tracts. Furthermore, we investigated the effect of fractional anisotropy (FA) thresholds for the tractography and identified FA values between 0.02 and 0.08 as optimal in our study. Last, we validated the course of entire tractography curves to move beyond correctness determination based on pairs of single points on a tract. Thus, histological techniques, in conjunction with alignment and processing tools, may serve as an important validation method of DW-MRI on the level of inferred tractography projections between brain areas.

High-Resolution Diffusion Tensor Imaging and Tractography of the Human Optic Chiasm at 9.4 T

The optic chiasm with its complex fiber micro-structure is a challenge for diffusion tensor models and tractography methods. Likewise, it is an ideal candidate for evaluation of diffusion tensor imaging tractography approaches in resolving inter-regional connectivity because the macroscopic connectivity of the optic chiasm is well known. Here, high-resolution (156 microm in-plane) diffusion tensor imaging of the human optic chiasm was performed ex vivo at ultra-high field (9.4 T). Estimated diffusion tensors at this high resolution were able to capture complex fiber configurations such as sharp curves, and convergence and divergence of tracts, but were unable to resolve directions at sites of crossing fibers. Despite the complex microstructure of the fiber paths through the optic chiasm, all known connections could be tracked by a line propagation algorithm. However, fibers crossing from the optic nerve to the contralateral tract were heavily underrepresented, whereas ipsilateral nerve-to-tract connections, as well as tract-to-tract connections, were overrepresented, and erroneous nerve-to-nerve connections were tracked. The effects of spatial resolution and the varying degrees of partial volume averaging of complex fiber architecture on the performance of these methods could be investigated. Errors made by the tractography algorithm at high resolution were shown to increase at lower resolutions closer to those used in vivo. This study shows that increases in resolution, made possible by higher field strengths, improve the accuracy of DTI-based tractography. More generally, post-mortem investigation of fixed tissue samples with diffusion imaging at high field strengths is important in the evaluation of MR-based diffusion models and tractography algorithms.

Differential effects of neurotrophins on ocular dominance plasticity in developing and adult cat visual cortex

In the present study we examine the influence of neurotrophins on experience‐dependent synaptic rearrangement in developing and adult visual cortex. Brain‐derived neurotrophic factor (BDNF) or nerve growth factor (NGF) was continuously infused into cortical area 18, and the functional architecture of the cortex was examined by use of optical and electrophysiological recording techniques. In kittens, BDNF infusion during monocular deprivation (MD) reversed the normally occurring ocular dominance (OD) shift towards the non‐deprived eye so that the deprived eye dominated the BDNF‐treated cortex after MD. Under conditions of equal activation of thalamocortical synapses, i.e. when animals were either subject to binocular deprivation (BD) or reared without deprivation, BDNF infusion did not disrupt binocularity of cortical units, but reversed the natural OD bias towards the contralateral eye in favour of the ipsilateral eye. In addition, BDNF treatment in kittens led to a loss of the orientation selectivity of cortical units irrespective of rearing conditions. In adult animals, BDNF influenced neither OD distributions nor orientation selectivity. The effect of NGF was markedly different. It was ineffective in kittens but in adult animals it caused a shift of OD towards the deprived eye when MD was combined with NGF infusion. However, in this case orientation selectivity was preserved. Thus, both neurotrophins have profound activity‐ and age‐dependent effects on the functional architecture of the visual cortex. Moreover, our results indicate that simple substitution of neurotrophins in excess is unlikely to compensate for deprivation effects by preserving or restoring the normal functional architecture of the cortex.

Histological validation of high-resolution DTI in human post mortem tissue

Diffusion tensor imaging (DTI) is amongst the simplest mathematical models available for diffusion magnetic resonance imaging, yet still by far the most used one. Despite the success of DTI as an imaging tool for white matter fibers, its anatomical underpinnings on a microstructural basis remain unclear. In this study, we used 65 myelin-stained sections of human premotor cortex to validate modeled fiber orientations and oft used microstructure-sensitive scalar measures of DTI on the level of individual voxels. We performed this validation on high spatial resolution diffusion MRI acquisitions investigating both white and gray matter. We found a very good agreement between DTI and myelin orientations with the majority of voxels showing angular differences less than 10°. The agreement was strongest in white matter, particularly in unidirectional fiber pathways. In gray matter, the agreement was good in the deeper layers highlighting radial fiber directions even at lower fractional anisotropy (FA) compared to white matter. This result has potentially important implications for tractography algorithms applied to high resolution diffusion MRI data if the aim is to move across the gray/white matter boundary. We found strong relationships between myelin microstructure and DTI-based microstructure-sensitive measures. High FA values were linked to high myelin density and a sharply tuned histological orientation profile. Conversely, high values of mean diffusivity (MD) were linked to bimodal or diffuse orientation distributions and low myelin density. At high spatial resolution, DTI-based measures can be highly sensitive to white and gray matter microstructure despite being relatively unspecific to concrete microarchitectural aspects.