Population decoding in rat barrel cortex: optimizing the linear readout of correlated population responses

Sensory information is encoded in the response of neuronal populations. How might this information be decoded by downstream neurons? Here we analyzed the responses of simultaneously recorded barrel cortex neurons to sinusoidal vibrations of varying amplitudes preceded by three adapting stimuli of 0, 6 and 12 µm in amplitude. Using the framework of signal detection theory, we quantified the performance of a linear decoder which sums the responses of neurons after applying an optimum set of weights. Optimum weights were found by the analytical solution that maximized the average signal-to-noise ratio based on Fisher linear discriminant analysis. This provided a biologically plausible decoder that took into account the neuronal variability, covariability, and signal correlations. The optimal decoder achieved consistent improvement in discrimination performance over simple pooling. Decorrelating neuronal responses by trial shuffling revealed that, unlike pooling, the performance of the optimal decoder was minimally affected by noise correlation. In the non-adapted state, noise correlation enhanced the performance of the optimal decoder for some populations. Under adaptation, however, noise correlation always degraded the performance of the optimal decoder. Nonetheless, sensory adaptation improved the performance of the optimal decoder mainly by increasing signal correlation more than noise correlation. Adaptation induced little systematic change in the relative direction of signal and noise. Thus, a decoder which was optimized under the non-adapted state generalized well across states of adaptation

Development of Gaussian Learning Algorithms for Early Detection of Alzheimer\u27s Disease

Alzheimer’s disease (AD) is the most common form of dementia affecting 10% of the population over the age of 65 and the growing costs in managing AD are estimated to be $259 billion, according to data reported in the 2017 by the Alzheimer\u27s Association. Moreover, with cognitive decline, daily life of the affected persons and their families are severely impacted. Taking advantage of the diagnosis of AD and its prodromal stage of mild cognitive impairment (MCI), an early treatment may help patients preserve the quality of life and slow the progression of the disease, even though the underlying disease cannot be reversed or stopped. This research aims to develop Gaussian learning algorithms, natural language processing (NLP) techniques, and mathematical models to effectively delineate the MCI participants from the cognitively normal (CN) group, and identify the most significant brain regions and patterns of changes associated with the progression of AD. The focus will be placed on the earliest manifestations of the disease (early MCI or EMCI) to plan for effective curative/therapeutic interventions and protocols. Multiple modalities of biomarkers have been found to be significantly sensitive in assessing the progression of AD. In this work, several novel multimodal classification frameworks based on proposed Gaussian Learning algorithms are created and applied to neuroimaging data. Classification based on the combination of structural magnetic resonance imaging (MRI), positron emission tomography (PET), and cerebrospinal fluid (CSF) biomarkers is seen as the most reliable approach for high-accuracy classification. Additionally, changes in linguistic complexity may provide complementary information for the diagnosis and prognosis of AD. For this research endeavor, an NLP-oriented neuropsychological assessment is developed to automatically analyze the distinguishing characteristics of text data in MCI group versus those in CN group. Early findings suggest significant linguistic differences between CN and MCI subjects in terms of word usage, vocabulary, recall, fragmented sentences. In summary, the results obtained indicate a high potential of the neuroimaging-based classification and NLP-oriented assessment to be utilized as a practically computer aided diagnosis system for classification and prediction of AD and its prodromal stages. Future work will ultimately focus on early signs of AD that could help in the planning of curative and therapeutic intervention to slow the progression of the disease

ECoG correlates of visuomotor transformation, neural plasticity, and application to a force-based brain computer interface

Electrocorticography: ECoG) has gained increased notoriety over the past decade as a possible recording modality for Brain-Computer Interface: BCI) applications that offers a balance of minimal invasiveness to the patient in addition to robust spectral information over time. More recently, the scale of ECoG devices has begun to shrink to the order of micrometer diameter contacts and millimeter spacings with the intent of extracting more independent signals for BCI control within less cortical real-estate. However, most control signals to date, whether within the field of ECoG or any of the more seasoned recording techniques, have translated their control signals to kinematic control parameters: i.e. position or velocity of an object) which may not be practical for certain BCI applications such as functional neuromuscular stimulation: FNS). Thus, the purpose of this dissertation was to present a novel application of ECoG signals to a force-based control algorithm and address its feasibility for such a BCI system. Micro-ECoG arrays constructed from thin-film polyimide were implanted epidurally over areas spanning premotor, primary motor, and parietal cortical areas of two monkeys: three hemispheres, three arrays). Monkeys first learned to perform a classic center-out task using a brain signal-to-velocity mapping for control of a computer cursor. The BCI algorithm utilized day-to-day adaptation of the decoding model to match the task intention of the monkeys with no need for pre-screeening of movement-related ECoG signals. Using this strategy, subjects showed notable 2-D task profiency and increased task-related modulation of ECoG features within five training sessions. After fixing the last model trained for velocity control of the cursor, the monkeys then utilized this decoding model to control the acceleration of the cursor in the same center-out task. Cursor movement profiles under this mapping paralleled those demonstrated using velocity control, and neural control signal profiles revealed the monkeys actively accelerated and decelerated the cursor within a limited time window: 1-1.5 seconds). The fixed BCI decoding model was recast once again to control the force on a virtual cursor in a novel mass-grab task. This task required targets not only to reach to peripheral targets but also account for an additional virtual mass as they grabbed each target and moved it to a second target location in the presence of the external force of gravity. Examination of the ensemble control signals showed neural adaptation to variations in the perceived mass of the target as well as the presence or absence of gravity. Finally, short rest periods were interleaved within blocks of each task type to elucidate differences between active BCI intention and rest. Using a post-hoc state-decoder model, periods of active BCI task control could be distinguished from periods of rest with a very high degree of accuracy: ~99%). Taken together, the results from these experiments present a first step toward the design of a dynamics-based BCI system suitable for FNS applications as well as a framework for implementation of an asyncrhonous ECoG BCI

Detection of Epileptogenic Cortical Malformations with Surface-Based MRI Morphometry

Magnetic resonance imaging has revolutionized the detection of structural abnormalities in patients with epilepsy. However, many focal abnormalities remain undetected in routine visual inspection. Here we use an automated, surface-based method for quantifying morphometric features related to epileptogenic cortical malformations to detect abnormal cortical thickness and blurred gray-white matter boundaries. Using MRI morphometry at 3T with surface-based spherical averaging techniques that precisely align anatomical structures between individual brains, we compared single patients with known lesions to a large normal control group to detect clusters of abnormal cortical thickness, gray-white matter contrast, local gyrification, sulcal depth, jacobian distance and curvature. To assess the effects of threshold and smoothing on detection sensitivity and specificity, we systematically varied these parameters with different thresholds and smoothing levels. To test the effectiveness of the technique to detect lesions of epileptogenic character, we compared the detected structural abnormalities to expert-tracings, intracranial EEG, pathology and surgical outcome in a homogeneous patient sample. With optimal parameters and by combining thickness and GWC, the surface-based detection method identified 92% of cortical lesions (sensitivity) with few false positives (96% specificity), successfully discriminating patients from controls 94% of the time. The detected structural abnormalities were related to the seizure onset zones, abnormal histology and positive outcome in all surgical patients. However, the method failed to adequately describe lesion extent in most cases. Automated surface-based MRI morphometry, if used with optimized parameters, may be a valuable additional clinical tool to improve the detection of subtle or previously occult malformations and therefore could improve identification of patients with intractable focal epilepsy who may benefit from surgery

Event-driven Similarity and Classification of Scanpaths

Eye tracking experiments often involve recording the pattern of deployment of visual attention over the stimulus as viewers perform a given task (e.g., visual search). It is useful in training applications, for example, to make available an expert\u27s sequence of eye movements, or scanpath, to novices for their inspection and subsequent learning. It may also be potentially useful to be able to assess the conformance of the novice\u27s scanpath to that of the expert. A computational tool is proposed that provides a framework for performing such classification, based on the use of a probabilistic machine learning algorithm. The approach was influenced by the need to compute similarity of eye fixations at single points in time, such as would be required for video stimuli. This method is also useful for eye movement analysis over static images and some interactive tasks. The algorithm employs a common qualitative omparison method, the heatmap, in a quantitative way to measure deviation from group aggregate behavior. This quantitative comparison is performed at individual events, defined by the stimulus, such as frame timestamps of video or mouseclicks of interactive tasks. The algorithm is evaluated and found to be more accurate and discriminative than existing comparison algorithms for the stimuli used in the examined experiments

Supervised Clustering of Genes for Multi-Class Phenotype Classification

The paper presents the new approach to the supervised gene selection by means of gene clustering for the microarray data, which belong to more than two phenotypes (classes). The main distinction from the previous approaches, that are based on the splitting the multi-class task into several binary ones, is the application of the HUM (hypervolume under the manifold) score, that guides the search for the most discriminative gene clusters that simultaneously differentiate all the classes. The results of comparative analysis with other methods shows the advantages of our approach both in classification rate of the new samples and in the lower number of gene clusters. The application of our approach to a randomly permuted data shows that the identified structure is more than just a noise artifact