Contributions of Dorsal/Ventral Hippocampus and Dorsolateral/Dorsomedial Striatum to Interval Timing

Humans and animals have remarkable capabilities in keeping time and using time as a guide to orient their learning and decision making. Psychophysical models of timing and time perception have been proposed for decades and have received behavioral, anatomical and pharmacological data support. However, despite numerous studies that aimed at delineating the neural underpinnings of interval timing, a complete picture of the neurobiological network of timing in the seconds-to-minutes range remains elusive. Based on classical interval timing protocols and proposing a Timing, Immersive Memory and Emotional Regulation (TIMER) test battery, the author investigates the contributions of the dorsal and ventral hippocampus as well as the dorsolateral and the dorsomedial striatum to interval timing by comparing timing performances in mice after they received cytotoxic lesions in the corresponding brain regions. On the other hand, a timing-based theoretical framework for the emergence of conscious experience that is closely related to the function of the claustrum is proposed so as to serve both biological guidance and the research and evolution of “strong” artificial intelligence. Finally, a new “Double Saturation Model of Interval Timing” that integrates the direct- and indirect- pathways of striatum is proposed to explain the set of empirical findings.

Quantitative Analysis of Kilohertz-Frequency Neurostimulation

Mainstream electrical stimulation therapies, e.g., spinal cord stimulation (SCS) and deep brain stimulation, use pulse trains that are delivered at rates no higher than 200 Hz. In recent years, stimulation of nerve fibers using kilohertz-frequency (KHF) signals has received increased attention due to the potential to penetrate deeper in the tissue and to the ability to block conduction of action potentials. As well, there are a growing number of clinical applications that use KHF waveforms, including transcutaneous electrical stimulation (TES) for overactive bladder and SCS for chronic pain. However, there is a lack of fundamental understanding of the mechanisms of action of KHF stimulation. The goal of this research was to analyze quantitatively KHF neurostimulation.

We implemented a multilayer volume conductor model of TES including dispersion and capacitive effects, and we validated the model with in vitro measurements in a phantom constructed from dispersive materials. We quantified the effects of frequency on the distribution of potentials and fiber excitation. We also quantified the effects of a novel transdermal amplitude modulated signal (TAMS) consisting of a non-zero offset sinusoidal carrier modulated by a square-pulse train. The model revealed that high-frequency signals generated larger potentials at depth than did low frequencies, but this did not translate into lower stimulation thresholds. Both TAMS and conventional rectangular pulses activated more superficial fibers in addition to the deeper, target fibers, and at no frequency did we observe an inversion of the strength-distance relationship. In addition, we performed in vivo experiments and applied direct stimulation to the sciatic nerve of cats and rats. We measured electromyogram and compound action potential activity evoked by pulses, TAMS and modified versions of TAMS in which we varied the amplitude of the carrier. Nerve fiber activation using TAMS showed no difference with respect to activation with conventional pulse for carrier frequencies of 20 kHz and higher, regardless the size of the carrier. Therefore, TAMS with carrier frequencies >20 kHz does not offer any advantage over conventional pulses, even with larger amplitudes of the carrier, and this has implications for design of waveforms for efficient and effective TES.

We developed a double cable model of a dorsal column (DC) fiber to quantify the responses of DC fibers to a novel KHF-SCS signal. We validated the model using in vivo recordings of the strength-duration relationship and the recovery cycle of single DC fibers. We coupled the fiber model to a model of SCS in human and applied the KHF-SCS signal to quantify thresholds for activation and conduction block for different fiber diameters at different locations in the DCs. Activation and block thresholds increased sharply as the fibers were placed deeper in the DCs, and decreased for larger diameter fibers. Activation thresholds were > 5 mA in all cases and up to five times higher than for conventional (~ 50 Hz) SCS. For fibers exhibiting persistent activation, the degree of synchronization of the firing activity to the KHF-SCS signal, as quantified using the vector strength, was low for a broad amplitude range, and the dissimilarity between the activities in pairs of fibers, as quantified using the spike time distance, was high and decreased for more closely positioned fibers. Conduction block thresholds were higher than 30 mA for all fiber diameters at any depth and well above the amplitudes used clinically (0.5 – 5 mA). KHF-SCS appears to activate few, large, superficial fibers, and the activated fibers fire asynchronously to the stimulation signal and to other activated fibers.

The outcomes of this work contribute to the understanding of KHF neurostimulation by establishing the importance of the tissue filtering properties on the distribution of potentials, assessing quantitatively the impact of KHF stimulation on nerve fiber excitation, and developing and validating a detailed model of a DC fiber to characterize the effects of KHF stimulation on DC axons. The results have implications for design of waveforms for efficient and effective nerve fiber stimulation in the peripheral and central nervous system.

Into the Bends of Time and Musical Forces in Jazz: Group Interaction and Double-time in “My Foolish Heart” as performed by the Bill Evans Trio with Scott LaFaro and Paul Motian.

Into the Bends of Time is a 40-minute work in seven movements for a large chamber orchestra with electronics, utilizing real-time computer-assisted processing of music performed by live musicians. The piece explores various combinations of interactive relationships between players and electronics, ranging from relatively basic processing effects to musical gestures achieved through stages of computer analysis, in which resulting sounds are crafted according to parameters of the incoming musical material. Additionally, some elements of interaction are multi-dimensional, in that they rely on the participation of two or more performers fulfilling distinct roles in the interactive process with the computer in order to generate musical material. Through processes of controlled randomness, several electronic effects induce elements of chance into their realization so that no two performances of this work are exactly alike. The piece gets its name from the notion that real-time computer-assisted processing, in which sound pressure waves are transduced into electrical energy, converted to digital data, artfully modified, converted back into electrical energy and transduced into sound waves, represents a “bending” of time.

The Bill Evans Trio featuring bassist Scott LaFaro and drummer Paul Motian is widely regarded as one of the most important and influential piano trios in the history of jazz, lauded for its unparalleled level of group interaction. Most analyses of Bill Evans’ recordings, however, focus on his playing alone and fail to take group interaction into account. This paper examines one performance in particular, of Victor Young’s “My Foolish Heart” as recorded in a live performance by the Bill Evans Trio in 1961. In Part One, I discuss Steve Larson’s theory of musical forces (expanded by Robert S. Hatten) and its applicability to jazz performance. I examine other recordings of ballads by this same trio in order to draw observations about normative ballad performance practice. I discuss meter and phrase structure and show how the relationship between the two is fixed in a formal structure of repeated choruses. I then develop a model of perpetual motion based on the musical forces inherent in this structure. In Part Two, I offer a full transcription and close analysis of “My Foolish Heart,” showing how elements of group interaction work with and against the musical forces inherent in the model of perpetual motion to achieve an unconventional, dynamic use of double-time. I explore the concept of a unified agential persona and discuss its role in imparting the song’s inherent rhetorical tension to the instrumental musical discourse.