Laminar neural dynamics of auditory evoked responses: Computational modeling of local field potentials in auditory cortex of non-human primates.

Evoked neural responses to sensory stimuli have been extensively investigated in humans and animal models both to enhance our understanding of brain function and to aid in clinical diagnosis of neurological and neuropsychiatric conditions. Recording and imaging techniques such as electroencephalography (EEG), magnetoencephalography (MEG), local field potentials (LFPs), and calcium imaging provide complementary information about different aspects of brain activity at different spatial and temporal scales. Modeling and simulations provide a way to integrate these different types of information to clarify underlying neural mechanisms. In this study, we aimed to shed light on the neural dynamics underlying auditory evoked responses by fitting a rate-based model to LFPs recorded via multi-contact electrodes which simultaneously sampled neural activity across cortical laminae. Recordings included neural population responses to best-frequency (BF) and non-BF tones at four representative sites in primary auditory cortex (A1) of awake monkeys. The model considered major neural populations of excitatory, parvalbumin-expressing (PV), and somatostatin-expressing (SOM) neurons across layers 2/3, 4, and 5/6. Unknown parameters, including the connection strength between the populations, were fitted to the data. Our results revealed similar population dynamics, fitted model parameters, predicted equivalent current dipoles (ECD), tuning curves, and lateral inhibition profiles across recording sites and animals, in spite of quite different extracellular current distributions. We found that PV firing rates were higher in BF than in non-BF responses, mainly due to different strengths of tonotopic thalamic input, whereas SOM firing rates were higher in non-BF than in BF responses due to lateral inhibition. In conclusion, we demonstrate the feasibility of the model-fitting approach in identifying the contributions of cell-type specific population activity to stimulus-evoked LFPs across cortical laminae, providing a foundation for further investigations into the dynamics of neural circuits underlying cortical sensory processing.

Validation of tractography: Comparison with manganese tracing.

In this study, we used invasive tracing to evaluate white matter tractography methods based on ex vivo diffusion-weighted magnetic resonance imaging (dwMRI) data. A representative selection of tractography methods were compared to manganese tracing on a voxel-wise basis, and a more qualitative assessment examined whether, and to what extent, certain fiber tracts and gray matter targets were reached. While the voxel-wise agreement was very limited, qualitative assessment revealed that tractography is capable of finding the major fiber tracts, although there were some differences between the methods. However, false positive connections were very common and, in particular, we discovered that it is not possible to achieve high sensitivity (i.e., few false negatives) and high specificity (i.e., few false positives) at the same time. Closer inspection of the results led to the conclusion that these problems mainly originate from regions with complex fiber arrangements or high curvature and are not easily resolved by sophisticated local models alone. Instead, the crucial challenge in making tractography a truly useful and reliable tool in brain research and neurology lies in the acquisition of better data. In particular, the increase of spatial resolution, under preservation of the signal-to-noise-ratio, is key.

Diffusion imaging-based subdivision of the human hypothalamus: a magnetic resonance study with clinical implications.

The hypothalamus and its subdivisions are involved in many neuropsychiatric conditions such as affective disorders, schizophrenia, or narcolepsy, but parcellations of hypothalamic subnuclei have hitherto been feasible only with histological techniques in postmortem brains. In an attempt to map subdivisions of the hypothalamus in vivo, we analyzed the directionality information from high-resolution diffusion-weighted magnetic resonance images of healthy volunteers. We acquired T1-weighted and diffusion-weighted scans in ten healthy subjects at 3 T. In the T1-weighted images, we manually delineated an individual mask of the hypothalamus in each subject and computed in the co-registered diffusion-weighted images the similarity of the principal diffusion direction for each pair of mask voxels. By clustering the similarity matrix into three regions with a k-means algorithm, we obtained an anatomically coherent arrangement of subdivisions across hemispheres and subjects. In each hypothalamus mask, we found an anterior region with dorsoventral principal diffusion direction, a posteromedial region with rostro-caudal direction, and a lateral region with mediolateral direction. A comparative analysis with microstructural hypothalamus parcellations from the literature reveals that each of these regions corresponds to a specific group of hypothalamic subnuclei as defined in postmortem brains. This is to our best knowledge the first in vivo study that attempts a delineation of hypothalamic subdivisions by clustering diffusion-weighted magnetic resonance imaging data. When applied in a larger sample of neuropsychiatric patients, a structural analysis of hypothalamic subnuclei should contribute to a better understanding of the pathogenesis of neuropsychiatric conditions such as affective disorders.

Processing of pitch and time sequences in music.

Pitch and duration -- either as written symbols or in auditory form -- are the basic structural properties in tones that form a melodic sequence. From the cognitive perspective, it is still a matter of debate whether, and at which processing stage, these two factors are processed independently or interdependently. The present study addresses this issue from the neuroscientist's point of view by measuring event-related potentials (ERPs) in musicians and non-musicians. Either the pitches or the durations of the tones, or both, were permuted randomly over a set of melodies in order to remove all sequential ordering with respect to these factors. Effects of both, pitch and time order, on the peak amplitudes of the P1-N1-P2 complex were observed. ANOVA revealed that sequential processing may depend on the different levels of skill in analytical hearing. For musicians, strong interaction effects for all three ERP components corroborated the interdependence of pitch and time processing. Musicians also seem to rely on coherent time structure more than non-musicians and showed enlarged P1 and P2 components whenever tone duration, either with or without preserved pitch, was at random. Non-musicians tend to use ordered pitch relations for perceptual orientation, and main effects without any interactions might indicate some kind of independent processing of both dimensions at some processing stages.

The perception of musical phrase structure: a cross-cultural ERP study.

Electroencephalography (EEG) was used in a cross-cultural music study investigating phrase boundary perception. Chinese and German musicians performed a cultural categorization task under Chinese and Western music listening conditions. Western music was the major subject for both groups of musicians, while Chinese music was familiar to Chinese subjects only. By manipulating the presence of pauses between two phrases in the biphrasal melodies, EEG correlates for the perception of phrase boundaries were found in both groups under both music listening conditions. Between 450 and 600 ms, the music CPS (closure positive shift), which had been found in earlier studies with a false tone detection task, was replicated for the more global categorization task and for all combinations of subject group and musical style. At short latencies (100 and 450 ms post phrase boundary offset), EEG correlates varied as a function of musical styles and subject group. Both bottom-up (style properties of the music) and top-down (acculturation of the subjects) information interacted during this early processing stage.