Faculty Bibliography

Deficient cognitive top-down executive control has long been hypothesized to underlie inattention and impulsivity in attention-deficit/hyperactivity disorder (ADHD). However, top-down cognitive dysfunction explains a modest proportion of the ADHD phenotype whereas the salience of emotional dysregulation is being noted increasingly. Together, these two types of dysfunction have the potential to account for more of the phenotypic variance in patients diagnosed with ADHD. We develop this idea and suggest that top-down dysregulation constitutes a gradient extending from mostly non-emotional top-down control processes (i.e., "cool" executive functions) to mainly emotional regulatory processes (including "hot" executive functions). While ADHD has been classically linked primarily to the former, conditions involving emotional instability such as borderline and antisocial personality disorder are closer to the other. In this model, emotional subtypes of ADHD are located at intermediate levels of this gradient. Neuroanatomically, gradations in "cool" processing appear to be related to prefrontal dysfunction involving dorsolateral prefrontal cortex (dlPFC) and caudal anterior cingulate cortex (cACC), while "hot" processing entails orbitofrontal cortex and rostral anterior cingulate cortex (rACC). A similar distinction between systems related to non-emotional and emotional processing appears to hold for the basal ganglia (BG) and the neuromodulatory effects of the dopamine system. Overall we suggest that these two systems could be divided according to whether they process non-emotional information related to the exteroceptive environment (associated with "cool" regulatory circuits) or emotional information related to the interoceptive environment (associated with "hot" regulatory circuits). We propose that this framework can integrate ADHD, emotional traits in ADHD, borderline and antisocial personality disorder into a related cluster of mental conditions.

Introduction: Delayed sleep and meal timing promote metabolic dysregulation and obesity. Altered coordination of sleep and eating may impact food reward valuation in the brain; yet the independent and collective contribution of sleep and meal times remains unknown. This pilot, randomized crossover study manipulates both sleep and meal times while preserving normal sleep duration (8 h time in bed for 5 nights) to test how misalignment of sleeping and eating behaviors affects intrinsic functional connectivity (iFC) across reward and interoception-related brain circuitry. Methods: Resting state functional MRI scans (3T Siemens Skyra; TR = 2.5s; 2 x ~5-minute runs) were obtained for 4 participants (3 males; 25.3 +/- 4.6 years) who completed all 4 phases (normal sleep/normal meal; late sleep/normal meal; normal sleep/late meal; late sleep/late meal). Normal meal times were 1, 5, 11, and 12.5 h after awakening and late meal times were 4.5, 8.5, 14.5 and 16 h after awakening. For a priori selected regions-of-interest (seeds) relevant to food reward and interoception, each seed's iFC was calculated as the correlation between its time-series and that of every voxel, and then contrasted between conditions. Standard preprocessing and seed-based correlations used the Configurable Pipeline for the Analysis of Connectomes v0.3.9. Results: Statistically significant (p late) additionally significantly modulated iFC between left ventral striatum and precuneus. Other significant iFC modulations of components of reward and interoception circuitry will also be presented. Conclusion: These pilot findings provide support that misalignment of sleep and food timing alters iFC in regions relevant to food reward and interoception, motivating examination in a larger sample

With advanced aging, there is a decline in innate cardiovascular function. This decline is not general in nature. Instead, specific changes occur that impact the basic cardiovascular function, which include alterations in biochemical pathways and ion channel function. This review focuses on a particular ion channel that couple the latter two processes, namely the KATP channel, which opening is promoted by alterations in intracellular energy metabolism. We show that the intrinsic properties of the KATP channel changes with advanced aging and argue that the channel can be further modulated by biochemical changes. The importance is widespread, given the ubiquitous nature of the KATP channel in the cardiovascular system where it can regulate processes as diverse as cardiac function, blood flow and protection mechanisms against superimposed stress, such as cardiac ischemia. We highlight questions that remain to be answered before the KATP channel can be considered as a viable target for therapeutic intervention.

How stem cells produce the huge diversity of neurons that form the visual system, and how these cells are assembled in neural circuits are a critical question in developmental neurobiology. Investigations in Drosophila have led to the discovery of several basic principles of neural patterning. In this chapter, we provide an overview of the field by describing the development of the Drosophila visual system, from the embryo to the adult and from the gross anatomy to the cellular level. We then explore the general molecular mechanisms identified that might apply to other neural structures in flies or in vertebrates. Finally, we discuss the major challenges that remain to be addressed in the field.

Diverse translational and research applications could benefit from the noninvasive ability to reversibly modulate (excite or suppress) CNS activity using ultrasound pulses, however, without clarifying the underlying mechanism, advanced design-based ultrasonic neuromodulation remains elusive. Recently, intramembrane cavitation within the bilayer membrane was proposed to underlie both the biomechanics and the biophysics of acoustic bio-effects, potentially explaining cortical stimulation results through a neuronal intramembrane cavitation excitation (NICE) model. Here, NICE theory is shown to provide a detailed predictive explanation for the ability of ultrasonic (US) pulses to also suppress neural circuits through cell-type-selective mechanisms: according to the predicted mechanism T-type calcium channels boost charge accumulation between short US pulses selectively in low threshold spiking interneurons, promoting net cortical network inhibition. The theoretical results fit and clarify a wide array of earlier empirical observations in both the cortex and thalamus regarding the dependence of ultrasonic neuromodulation outcomes (excitation-suppression) on stimulation and network parameters. These results further support a unifying hypothesis for ultrasonic neuromodulation, highlighting the potential of advanced waveform design for obtaining cell-type-selective network control.