Faculty Bibliography

The local field potential (LFP) is an aggregate measure of group neuronal activity and is often correlated with the action potentials of single neurons. In recent years, investigators have found that action potential firing rates increase during elevations in power high-frequency band oscillations (50-200 Hz range). However, action potentials also contribute to the LFP signal itself, making the spike-LFP relationship complex. Here, we examine the relationship between spike rates and LFP in varying frequency bands in rat neocortical recordings. We find that 50-180 Hz oscillations correlate most consistently with high firing rates, but that other LFP bands also carry information relating to spiking, including in some cases anti-correlations. Relatedly, we find that spiking itself and electromyographic activity contribute to LFP power in these bands. The relationship between spike rates and LFP power varies between brain states and between individual cells. Finally, we create an improved oscillation-based predictor of action potential activity by specifically utilizing information from across the entire recorded frequency spectrum of LFP. The findings illustrate both caveats and improvements to be taken into account in attempts to infer spiking activity from LFP.

Engineered neural implants have a myriad of potential basic science and clinical neural repair applications. Although there are implants that are currently undergoing their first clinical investigations, optimizing their long-term viability and efficacy remain an open challenge. Functional implants with pre-vascularization of various engineered tissues have proven to enhance post-implantation host integration, and well-known synergistic neural-vascular interplays suggest that this strategy could also be promising for neural tissue engineering. Here, we report the development of a novel bio-engineered neuro-vascular co-culture construct, and demonstrate that it exhibits enhanced neurotrophic factor expression, and more complex neuronal morphology. Crucially, by introducing genetically encoded calcium indicators (GECIs) into the co-culture, we are able to monitor functional activity of the neural network, and demonstrate greater activity levels and complexity as a result of the introduction of endothelial cells in the construct. The presence of this enhanced activity could putatively lead to superior integration outcomes. Indeed, leveraging on the ability to monitor the construct's development post-implantation with GECIs, we observe improved integration phenotypes in the spinal cord of mice relative to non-vascularized controls. Our approach provides a new experimental system with functional neural feedback for studying the interplay between vascular and neural development while advancing the optimization of neural implants towards potential clinical applications.

Neural computations are often compared to instrument-measured distance or duration, and such relationships are interpreted by a human observer. However, neural circuits do not depend on human-made instruments but perform computations relative to an internally defined rate-of-change. While neuronal correlations with external measures, such as distance or duration, can be observed in spike rates or other measures of neuronal activity, what matters for the brain is how such activity patterns are utilized by downstream neural observers. We suggest that hippocampal operations can be described by the sequential activity of neuronal assemblies and their internally defined rate of change without resorting to the concept of space or time.

Aggression is a fundamental social behavior that is essential for competing for resources and protecting oneself and families in both males and females. As a result of natural selection, aggression is often displayed differentially between the sexes, typically at a higher level in males than females. Here, we highlight the behavioral differences between male and female aggression in rodents. We further outline the aggression circuits in males and females, and compare their differences at each circuit node. Lastly, we summarize our current understanding regarding the generation of sexually dimorphic aggression circuits during development and their maintenance during adulthood. In both cases, gonadal steroid hormones appear to play crucial roles in differentiating the circuits by impacting on the survival, morphology, and intrinsic properties of relevant cells. Many other factors, such as environment and experience, may also contribute to sex differences in aggression and remain to be investigated in future studies.

In many studies of attention-deficit hyperactivity disorder (ADHD), stimulus encoding and processing (perceptual function) and response selection (executive function) have been intertwined. To dissociate deficits in these functions, we introduced a task that parametrically varied low-level stimulus features (orientation and color) for fine-grained analysis of perceptual function. It also required participants to switch their attention between feature dimensions on a trial-by-trial basis, thus taxing executive processes. Furthermore, we used a response paradigm that captured task-irrelevant motor output (TIMO), reflecting failures to use the correct stimulus-response rule. ADHD participants had substantially higher perceptual variability than controls, especially for orientation, as well as higher TIMO. In both ADHD and controls, TIMO was strongly affected by the switch manipulation. Across participants, the perceptual variability parameter was correlated with TIMO, suggesting that perceptual deficits are associated with executive function deficits. Based on perceptual variability alone, we were able to classify participants into ADHD and controls with a mean accuracy of about 77%. Participants' self-reported General Executive Composite score correlated not only with TIMO but also with the perceptual variability parameter. Our results highlight the role of perceptual deficits in ADHD and the usefulness of computational modeling of behavior in dissociating perceptual from executive processes.

Patients with hereditary sensory and autonomic neuropathy type III(HSAN III) exhibit marked gait disturbances. The cause of the gaitataxia is not known, but we recently showed that functional musclespindle afferents in the leg, recorded via intraneural microelectrodesinserted into the peroneal nerve, are absent in HSAN III, althoughlarge-diameter cutaneous afferents are intact. Moreover, there is atight correlation between loss of proprioceptive acuity at the knee andthe severity of gait impairment. Here we tested the hypothesis thatmanual motor performance is also compromised in HSAN III,attributed to the predicted absence of muscle spindles in the intrinsicmuscles of the hand. Manual performance in the Purdue pegboardtask was assessed in 12 individuals with HSAN III and 12 age-matched healthy controls. The mean (+/- SD) pegboard score (number ofpins inserted in 30 s) was 8.1 +/- 1.9 and 8.6 +/- 1.8 for the left andright hand respectively, significantly lower than the scores for thecontrols (14.3 +/- 2.9 and 15.5 +/- 2.0; P <0.0001). In five patients weinserted a tungsten microelectrode into the ulnar nerve at the wrist.No spontaneous or stretch-evoked muscle afferent activity could beidentified in any of the 11 fascicles supplying intrinsic muscles of thehand, whereas rich tactile afferent activity could be recorded from 4cutaneous fascicles. We conclude that functional muscle spindles areabsent in the hand, and likely absent in the long finger flexors andextensors, and that this largely accounts for the poor manual motorperformance in HSAN III

INTRODUCTION/BACKGROUND:-weighted DCE-MRI. MATERIALS AND METHODS/METHODS:) and arterial input function (AIF). In addition, the effect of the conversion method on the diagnostic accuracy was evaluated with 36 breast lesions (19 benign and 17 malignant). RESULTS:. CONCLUSION/CONCLUSIONS:measurement is not available and a low FA is used for DCE-MRI, the uncertainty in the contrast kinetic parameter estimation can be reduced by using the LC method with pAIF, without compromising the diagnostic accuracy.

Nervous systems control locomotion using rhythmically active networks that orchestrate motor neuron firing patterns. Whether animals use common or distinct genetic programs to encode motor rhythmicity remains unclear. Cross-species comparisons have revealed remarkably conserved neural patterning systems but have also unveiled divergent circuit architectures that can generate similar locomotor behaviors.