Greg T. Gdowski

Firing behaviour of squirrel monkey eye movement‐related vestibular nucleus neurons during gaze saccades

The firing behaviour of vestibular nucleus neurons putatively involved in producing the vestibulo‐ocular reflex (VOR) was studied during active and passive head movements in squirrel monkeys. Single unit recordings were obtained from 14 position‐vestibular (PV) neurons, 30 position‐vestibular‐pause (PVP) neurons and 9 eye‐head‐vestibular (EHV) neurons. Neurons were sub‐classified as type I or II based on whether they were excited or inhibited during ipsilateral head rotation. Different classes of cell exhibited distinctive responses during active head movements produced during and after gaze saccades. Type I PV cells were nearly as sensitive to active head movements as they were to passive head movements during saccades. Type II PV neurons were insensitive to active head movements both during and after gaze saccades. PVP and EHV neurons were insensitive to active head movements during saccadic gaze shifts, and exhibited asymmetric sensitivity to active head movements following the gaze shift. PVP neurons were less sensitive to ondirection head movements during the VOR after gaze saccades, while EHV neurons exhibited an enhanced sensitivity to head movements in their on direction. Vestibular signals related to the passive head movement were faithfully encoded by vestibular nucleus neurons. We conclude that central VOR pathway neurons are differentially sensitive to active and passive head movements both during and after gaze saccades due primarily to an input related to head movement motor commands. The convergence of motor and sensory reafferent inputs on VOR pathways provides a mechanism for separate control of eye and head movements during and after saccadic gaze shifts.

The neurophysiological substrate for the cervico-ocular reflex in the squirrel monkey.

Abstract. Passive rotation of the trunk with respect to the head evoked cervico-ocular reflex (COR) eye movements in squirrel monkeys. The amplitude of the reflex varied both within and between animals, but the eye movements were always in the same direction as trunk rotation. In the dark, the COR typically had a gain of 0.3–0.4. When animals fixated earth-stationary targets during low-frequency passive neck rotation or actively tracked moving visual targets with head movements, the COR was suppressed. The COR and vestibulo-ocular reflex (VOR) summed during passive head-on-trunk rotation producing compensatory eye movements whose gain was greater than 1.0. The firing behavior of VOR-related vestibular neurons and cerebellar flocculus Purkinje cells was studied during the COR. Passive neck rotation produced changes in firing rate related to neck position and/or neck velocity in both position-vestibular-pause neurons and eye-head-vestibular neurons, although the latter neurons were much more sensitive to the COR than the former. The neck rotation signals were reduced or reversed in direction when the COR was suppressed. Flocculus Purkinje cells were relatively insensitive to COR eye movements. However, when the COR was suppressed, their firing rate was modulated by neck rotation. These neck rotation signals summed with ocular pursuit signals when the head was used to pursue targets. We suggest that the neural substrate that produces the COR includes central VOR pathways, and that the flocculus plays an important role in suppressing the reflex when it would cause relative movement of a visual target on the retina.

Response map properties of units in the dorsal cochlear nucleus of barbiturate-anesthetized gerbil (Meriones unguiculatus)

The response map scheme introduced by Evans and Nelson (1973) and modified by others, including Davis et al. (1996) for use with gerbils, has been used primarily for classifying units recorded in the cochlear nucleus of unanesthetized decerebrate preparations. Units lacking spontaneous activity (SpAc) have been classified as either type I/III or type II units based on the relative strength of their responses to broad-band noise compared to their responses to best-frequency (BF) tones. The relative noise index (rho), a ratio of these responses after SpAc is subtracted out, provides a convenient measure of this relative strength. In this paper, responses of 320 units recorded in the dorsal cochlear nucleus (DCN) of barbiturate-anesthetized gerbils to short-duration BF tones and broad-band noise were recorded. Since 87.5% of these units lacked SpAc, their response maps resembled those of type II and type I/III units. Units were characterized by rho and the normalized slope (m) of a best line fit to the BF rate versus level plot starting from the sound level corresponding to the first inflection point of the rate curve (typically its maximum value or the start of its sloping saturation). The distributions of rho and m values do not form distinct clusters as they do for units in the decerebrate preparation. Thus, the criteria developed for classifying DCN units in the decerebrate preparation do not appear appropriate for units in the barbiturate-anesthetized preparation. Deposits of horseradish peroxidase were used to locate 52 units. Most of the low SpAc units, 56% with poor noise responses (5/9) and nearly 70% with strong noise responses (25/36), and nearly all of the high SpAc units (6/7), were located either within or below the fusiform cell layer.

A statistically based method to generate response maps objectively

One scheme to classify the physiological response properties of single units in the cochlear nucleus is based on the average discharge rate of the unit and is reflected in the distribution of excitatory and inhibitory regions in a frequency-level map (response map) that spans the units receptive area (e.g., Evans and Nelson, 1973; Young and Brownell, 1976; Young and Voigt, 1982; Shofner and Young, 1985, Spirou and Young, 1991). Typically, discharge rate versus level curves are acquired at many frequencies and the investigator determines that a unit is excited or inhibited at a given level if the driven rate is above or below a spontaneous rate estimate by a specified criterion (for example, 20%). The investigator then encloses regions of excitation and inhibition where responses over adjacent frequencies and levels are consistent. In the present report, we describe an objective 3-step computer-based method to generate response maps: raw driven and spontaneous rate estimates are smoothed with a low-pass spatial filter; a unit is said to be excited or inhibited at a given level if the filtered driven rate is above or below the mean filtered spontaneous rate for that frequency by a specified criterion (percentage or statistical); and resultant response maps are median spatial filtered to eliminate spurious regions. The results shown here demonstrate that use of a statistical criterion provides a more reliable detection of excitation and inhibition than a 20% criterion, particularly when the variance of the rate estimates is high. Further, the statistically based method permits unit classification based on response map data that are more rapidly acquired with shorter duration stimuli (32 vs. 200 ms). Although this method is applied to units recorded in the dorsal cochlear nucleus, the technique may be applicable to studies of receptive fields and their plasticity in other systems.

Photodynamic antimicrobial polymers for infection control

Hospital-acquired infections pose both a major risk to patient wellbeing and an economic burden on global healthcare systems, with the problem compounded by the emergence of multidrug resistant and biocide tolerant bacterial pathogens. Many inanimate surfaces can act as a reservoir for infection, and adequate disinfection is difficult to achieve and requires direct intervention. In this study we demonstrate the preparation and performance of materials with inherent photodynamic, surface-active, persistent antimicrobial properties through the incorporation of photosensitizers into high density poly(ethylene) (HDPE) using hot-melt extrusion, which require no external intervention except a source of visible light. Our aim is to prevent bacterial adherence to these surfaces and eliminate them as reservoirs of nosocomial pathogens, thus presenting a valuable advance in infection control. A two-layer system with one layer comprising photosensitizer-incorporated HDPE, and one layer comprising HDPE alone is also described to demonstrate the versatility of our approach. The photosensitizer-incorporated materials are capable of reducing the adherence of viable bacteria by up to 3.62 Log colony forming units (CFU) per square centimeter of material surface for methicillin resistant Staphylococcus aureus (MRSA), and by up to 1.51 Log CFU/cm2 for Escherichia coli. Potential applications for the technology are in antimicrobial coatings for, or materials comprising objects, such as tubing, collection bags, handrails, finger-plates on hospital doors, or medical equipment found in the healthcare setting.

Convergence of Vestibular and Neck Proprioceptive Sensory Signals in the Cerebellar Interpositus

The cerebellar interpositus nucleus (IN) contributes to controlling voluntary limb movements. We hypothesized that the vestibular signals within the IN might be transformed into coordinates describing the bodys movement, appropriate for controlling limb movement. We tested this hypothesis by recording from IN neurons in alert squirrel monkeys during vestibular and proprioceptive stimulation produced during (1) yaw head-on-trunk rotation about the C1–C2 axis while in an orthograde posture and (2) lateral side-to-side flexion about the C6–T3 axis while in a pronograde posture. Neurons (44/67) were sensitive to vestibular stimulation (23/44 to rotation and translation, 14/44 to rotation only, 7/44 to translation only). Most neurons responded during contralateral movement. Neurons (29/44) had proprioceptive responses; the majority (21/29) were activated during neck rotation and lateral flexion. In all 29 neurons with convergent vestibular and neck proprioceptive input those inputs functionally canceled each other during all combined sensory stimulation, whether in the orthograde or pronograde posture. These results suggest that two distinct populations of IN neurons exist, each of which has vestibular sensitivity. One population carries vestibular signals that describe the heads movement in space as is traditional for vestibular signals without proprioceptive signals. A second population of neurons demonstrated precise matching of vestibular and proprioceptive signals, even for complicated stimuli, which activated the semicircular canals and otolith organs and involved both rotation and flexion in the spine. Such neurons code body (not head) motion in space, which may be the appropriate platform for controlling limb movements.

Head movements produced during whole body rotations and their sensitivity to changes in head inertia in squirrel monkeys.

The heads inertia produces forces on the neck when the body moves. One collective function of the vestibulocollic and cervicocollic reflexes (VCR and CCR) is thought to be to stabilize the head with respect to the trunk during whole body movements. Little is known as to whether their head-movement kinematics produced by squirrel monkeys during whole body rotations are similar to those of cats and humans. Prior experiments with cats and human subjects have shown that yaw head-movement kinematics are unaffected by changes in the heads inertia when the whole body is rotated. These observations have led to the hypothesis that the combined actions of the VCR and CCR accommodate for changes in the heads inertia. To test this hypothesis in squirrel monkeys, it was imperative to first characterize the behavior of head movements produced during whole body rotation and then investigate their sensitivity to changes in the heads inertia. Our behavioral studies show that squirrel monkeys produce only small head movements with respect to the trunk during whole body rotations over a wide range of stimulus frequencies and velocities (0.5-4.0 Hz; 0-100 degrees /s). Similar head movements were produced when only small additional changes in the heads inertia occurred. Electromyographic recordings from the splenius muscle revealed that an active process was utilized such that increases in muscle activation occurred when the inertia of the head was increased. These results are consistent with prior cat and human studies, suggesting that squirrel monkeys have a similar horizontal VCR and CCR.

Reweighting Sensory Signals to Maintain Head Stability: Adaptive Properties of the Cervicocollic Reflex

A major goal of this study was to characterize the cervicocollic reflexes (CCRs) in awake squirrel monkeys and compare it to observations in cat. This was carried out by stabilizing the head in space while rotating the lower body. The magnitude and phase of the torque produced between the head and the restraint system was used as an indicator of the CCR. Many properties of the squirrel monkeys CCR were found to be similar to those of the cat. The torque decreased as a function of frequency and amplitude. In addition, the static level of torque increased with head eccentricity. One difference was that the torque was 90x smaller in squirrel monkeys. Biomechanical differences, such as differences in head inertia, could account for these differences. The second goal was to determine if the CCR was sensitive to increases in the heads inertia. To test this, we increased the heads inertia by a factor of 36 and allowed the reflexes to adapt by rotating the whole body while the head was free to move. The CCR was rapidly assessed by periodically stabilizing the head in space during whole-body rotations. The magnitude of the torque increased by nearly 60%, suggesting that the CCR may adapt when changes in the heads inertia are imposed. Changes in the torque were also consistent with changes in head-movement kinematics during whole-body rotation. This suggests that the collic reflexes may dynamically adapt to maintain the performance and kinematics of reflexive head movement.

Current concepts of vestibular nucleus function: transformation of vestibular signals in the vestibular nuclei.

Abstract: The vestibular nerve sends signals to the brain that code the movement and position of the head in space. These signals are used for a variety of functions, including the control of reflex and voluntary movements and the construction of a sense of self‐motion. In order to carry out these functions, sensory vestibular signals need to be transformed in a variety of ways. Transformations are thought to occur at an early stage of sensory processing in the brain, and in many cases are apparent in the responses of neurons in the vestibular nuclei that receive direct inputs from the vestibular nerve. Several specific examples of sensory transformation in the vestibular nuclei are presented, and current hypotheses about the mechanisms that are used to produce the transformations are discussed.

Measurement of upper limb kinematics and joint angle patterns during deep brain stimulation for parkinson’s disease

Therapeutic benefits of subthalamic nucleus (STN) deep brain stimulation (DBS) for motor symptoms of Parkinson’s disease (PD) are well-documented. However, the mechanisms underlying motor improvement with DBS remain poorly understood. We tested the hypothesis that STN-DBS-related improvements in voluntary arm movement kinematics are mediated by changes in the velocity and temporal sequencing of proximal joint angles. We evaluated a 56 year old male and 66 year old female with idiopathic Parkinson’s disease chronically implanted with bilateral STN-DBS. Patients performed a button press task while off medication in the DBS-on and DBS-off conditions. Movements of the upper limb were recorded using a 3D motion analysis system, and detailed kinematic measures were obtained for the arm and forearm. As expected, reaction and movement times were improved in the DBS-on compared to DBSoff condition. The two subjects differed with regards to the magnitude of their changes in peak linear velocity and peak angular velocities (shoulder flexion extension, shoulder abduction adduction and elbow flexion extension). Surprisingly, both PD patients increased the frequency with which they used a preferred sequence of shoulder and elbow joint activations when in the DBS-on condition. This preferred pattern was adopted with twice the frequency than in the DBS-off condition, and with increased frequency relative to a control group of 9 age-matched controls. These results suggest that STN-DBS may improve movement execution at the cost of flexibility in movement execution strategy.