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Biomedical subjects

Partha P Mitra

Publications and source records attributed to Partha P Mitra.

9 recordsLinked to original sources

The new frontier in understanding human and mammalian brain development.

Neurodevelopmental disorders that cause cognitive, behavioural or motor impairments affect around 15% of children and adolescents worldwide1, with diagnoses of profound autism and attention deficit hyperactivity disorder increasing in the USA and contributing to a major economic burden2,3. Yet the origins and mechanisms of these conditions remain poorly understood, limiting progress in therapies. Comprehensive cell atlases of the developing human brain, alongside those of model organisms such as mice and non-human primates, are now providing high-resolution measures of gene expression, cell-type abundance and spatial distribution. In this Perspective, we highlight recent studies that have identified novel developmental cell populations, revealed conserved and divergent patterns of cell genesis, migration and maturation across species, and begun testing hypotheses that link them to processes ranging from transcriptional control of cell fate specification to the emergence of complex behaviours. We present remaining conceptual and technical challenges and provide an outlook on how further studies of human and mammalian brain development can empower a deeper understanding of neurodevelopmental and neuropsychiatric disorders. Future efforts expanding to additional developmental stages, including adolescence, as well as whole-brain, multimodal and cross-species integration, will yield new insights into how development shapes the brain. These atlases promise to serve as essential references for unravelling mechanisms of brain function and disease vulnerability, and for advancing precision medicine.

Humans↗

Concentration maximization and local basis expansions (LBEX) for linear inverse problems.

Linear inverse problems arise in biomedicine electroencephalography and magnetoencephalography (EEG and MEG) and geophysics. The kernels relating sensors to the unknown sources are Green's functions of some partial differential equation. This knowledge is obscured when treating the discretized kernels simply as matrices. Consequently, physical understanding of the fundamental resolution limits has been lacking. We relate the inverse problem to spatial Fourier analysis, and the resolution limits to uncertainty principles, providing conceptual links to underlying physics. Motivated by the spectral concentration problem and multitaper spectral analysis, our approach constructs local basis sets using maximally concentrated linear combinations of the measurement kernels.

Algorithms↗

A method for detection and classification of events in neural activity.

We present a method for the real time prediction of punctuate events in neural activity, based on the time-frequency spectrum of the signal, applicable both to continuous processes like local field potentials (LFPs) as well as to spike trains. We test it on recordings of LFP and spiking activity acquired previously from the lateral intraparietal area (LIP) of macaque monkeys performing a memory-saccade task. In contrast to earlier work, where trials with known start times were classified, our method detects and classifies trials directly from the data. It provides a means to quantitatively compare and contrast the content of LFP signals and spike trains: we find that the detector performance based on the LFP matches the performance based on spike rates. The method should find application in the development of neural prosthetics based on the LFP signal. Our approach uses a new feature vector, which we call the 2d cepstrum.

Algorithms↗

Dynamic phenotypes: time series analysis techniques for characterizing neuronal and behavioral dynamics.

We consider quantitative measures of behavioral and neuronal dynamics as a means of characterizing phenotypes. Such measures are important from a scientific perspective; because understanding brain function is contingent on understanding the link between the dynamics of the nervous system and behavioral dynamics. They are also important from a biomedical perspective because they provide a contrast to purely psychological characterizations of phenotype or characterizations via static brain images or maps, and are a potential means for differential diagnoses of neuropsychiatric illnesses. After a brief presentation of background work and some current advances, we suggest that more attention needs to be paid to dynamic characterizations of phenotypes. We will discuss some of the relevant time series analysis tools.

Action Potentials↗

Gamma-band synchronization in visual cortex predicts speed of change detection.

Our capacity to process and respond behaviourally to multiple incoming stimuli is very limited. To optimize the use of this limited capacity, attentional mechanisms give priority to behaviourally relevant stimuli at the expense of irrelevant distractors. In visual areas, attended stimuli induce enhanced responses and an improved synchronization of rhythmic neuronal activity in the gamma frequency band (40-70 Hz). Both effects probably improve the neuronal signalling of attended stimuli within and among brain areas. Attention also results in improved behavioural performance and shortened reaction times. However, it is not known how reaction times are related to either response strength or gamma-band synchronization in visual areas. Here we show that behavioural response times to a stimulus change can be predicted specifically by the degree of gamma-band synchronization among those neurons in monkey visual area V4 that are activated by the behaviourally relevant stimulus. When there are two visual stimuli and monkeys have to detect a change in one stimulus while ignoring the other, their reactions are fastest when the relevant stimulus induces strong gamma-band synchronization before and after the change in stimulus. This enhanced gamma-band synchronization is also followed by shorter neuronal response latencies on the fast trials. Conversely, the monkeys' reactions are slowest when gamma-band synchronization is high in response to the irrelevant distractor. Thus, enhanced neuronal gamma-band synchronization and shortened neuronal response latencies to an attended stimulus seem to have direct effects on visually triggered behaviour, reflecting an early neuronal correlate of efficient visuo-motor integration.

Animals↗

How sleep affects the developmental learning of bird song.

Sleep affects learning and development in humans and other animals, but the role of sleep in developmental learning has never been examined. Here we show the effects of night-sleep on song development in the zebra finch by recording and analysing the entire song ontogeny. During periods of rapid learning we observed a pronounced deterioration in song structure after night-sleep. The song regained structure after intense morning singing. Daily improvement in similarity to the tutored song occurred during the late phase of this morning recovery; little further improvement occurred thereafter. Furthermore, birds that showed stronger post-sleep deterioration during development achieved a better final imitation. The effect diminished with age. Our experiments showed that these oscillations were not a result of sleep inertia or lack of practice, indicating the possible involvement of an active process, perhaps neural song-replay during sleep. We suggest that these oscillations correspond to competing demands of plasticity and consolidation during learning, creating repeated opportunities to reshape previously learned motor skills.

Acoustic Stimulation↗

Multiple neural spike train data analysis: state-of-the-art and future challenges.

Multiple electrodes are now a standard tool in neuroscience research that make it possible to study the simultaneous activity of several neurons in a given brain region or across different regions. The data from multi-electrode studies present important analysis challenges that must be resolved for optimal use of these neurophysiological measurements to answer questions about how the brain works. Here we review statistical methods for the analysis of multiple neural spike-train data and discuss future challenges for methodology research.

Action Potentials↗

Neural prosthetic control signals from plan activity.

The prospect of assisting disabled patients by translating neural activity from the brain into control signals for prosthetic devices, has flourished in recent years. Current systems rely on neural activity present during natural arm movements. We propose here that neural activity present before or even without natural arm movements can provide an important, and potentially advantageous, source of control signals. To demonstrate how control signals can be derived from such plan activity we performed a computational study with neural activity previously recorded from the posterior parietal cortex of rhesus monkeys planning arm movements. We employed maximum likelihood decoders to estimate movement direction and to drive finite state machines governing when to move. Performance exceeded 90% with as few as 40 neurons.

Action Potentials↗

Temporal structure in neuronal activity during working memory in macaque parietal cortex.

Many cortical structures have elevated firing rates during working memory, but it is not known how the activity is maintained. To investigate whether reverberating activity is important, we studied the temporal structure of local field potential (LFP) activity and spiking from area LIP in two awake macaques during a memory-saccade task. Using spectral analysis, we found spatially tuned elevated power in the gamma band (25-90 Hz) in LFP and spiking activity during the memory period. Spiking and LFP activity were also coherent in the gamma band but not at lower frequencies. Finally, we decoded LFP activity on a single-trial basis and found that LFP activity in parietal cortex discriminated between preferred and anti-preferred direction with approximately the same accuracy as the spike rate and predicted the time of a planned movement with better accuracy than the spike rate. This finding could accelerate the development of a cortical neural prosthesis.

Action Potentials↗