Adaptation Time Constant Research Articles

The Endogenous Calcium Buffer and the Time Course of Transducer Adaptation in Auditory Hair Cells

Mechanoelectrical transducer currents in turtle auditory hair cells adapt to maintained stimuli via a Ca2+-dependent mechanism that is sensitive to the level of internal calcium buffer. We have used the properties of transducer adaptation to compare the effects of exogenous calcium buffers in the patch electrode solution with those of the endogenous buffer assayed with perforated-patch recording. The endogenous buffer of the hair bundle was equivalent to 0.1-0.4 mM BAPTA and, in a majority of cells, supported adaptation in an external Ca2+ concentration of 70 microM similar to that in turtle endolymph. The endogenous buffer had a higher effective concentration, and the adaptation time constant was faster in cells at the high-frequency end than at the low-frequency end of the cochlea. Experiments using buffers with different Ca2+-binding rates or dissociation constants indicated that the speed of adaptation and the resting open probability of the transducer channels could be differentially regulated and imply that the endogenous buffer must be a fast, high-affinity buffer. In some hair cells, the transducer current did not decay exponentially during a sustained stimulus but displayed damped oscillations at a frequency (58-230 Hz) that depended on external Ca2+ concentration. The gradient in adaptation time constant and the tuned transducer current at physiological levels of calcium buffer and external Ca2+ suggest that transducer adaptation may contribute to hair cell frequency selectivity. The results are discussed in terms of feedback regulation of transducer channels mediated by Ca2+ binding at two intracellular sites.

Temporal aspects of the effects of cooling on responses of single auditory nerve fibers

During an investigation of the effects of cochlear cooling on frequency tuning and input/output relations of single auditory nerve fibers in gerbil (Ohlemiller and Siegel (1994) Hear. Res. 80, 174–190), cooling-related changes in post-stimulus time histogram (PSTH) shape and phase-locking to tonebursts were characterized in a small sample of neurons. Local cochlear cooling by 5–10°C below normal core temperature did not alter overall PSTH shape, although some evidence was found for a reduction in the time constants of rapid and short term rate adaptation. The relative contributions of rapid and short term response components appeared unaltered. Effects of cooling on phase-locking were assessed by calculating the synchronization index for responses to intense (>70 dB SPL) tonebursts at 0.5, 1.0, and 2.0 kHz. Synchronization filter functions exhibited modest reductions in both magnitude and the upper frequency limit of phase-locking. The effects of cooling on the temporal character of responses appear distinct from those of a simple reduction in stimulus intensity. Results are interpreted in terms of cooling-related changes in responses of cochlear hair cells and afferent neurons, and suggest that temperature artifacts are unlikely to underlie reported species differences in PSTH shape and phase-locking.

Robust control of induction motor drive with rotor time-constant adaptation

In this paper, an indirect field-oriented induction motor drive with a rotor time-constant adaptation is presented. Since the deviated rotor time-constant of an induction motor makes the indirect field-orientation inaccurate, an adaptation mechanism is proposed to tune the rotor time-constant to establish a complete indirect field-oriented control for an induction motor drive. With the rotor time-constant adaptation, the indirect field-oriented control has the robustness property for decoupling torque and flux components. In order to further insure the robustness of the servo control, a novel variable-structure speed controller is proposed under the adaptive field-orientation operation. A novel sliding surface with an integral component for the variable structure speed controller is designed, and exponential convergence in speed-tracking control is obtained. Using the proposed variable-structure speed controller, the insensitivity for parameter uncertainty and disturbance load is provided. Finally, a simulation and experimental results are demonstrated.

The frequency dependence of receptor potentials in hair cells of the mouse utricle

The mechanoelectrical transduction currents of hair cells in the mouse utricle adapt at varying rates to step deflections of the hair bundles. We consider contributions of this adaptation process and of input resistance and membrane capacitance to the frequency dependence of the receptor potential. Whole-cell recordings of transduction current and receptor potential were made from hair cells in the excised epithelium of the mouse utricle. Hair bundles were deflected by a fluid jet with step and sinusoidal waveforms. In type II cells, the receptor potential was a bandpass function of stimulus frequency. The adaptation rate of the transduction current, measured in response to step bundle deflections, accounted for much of the roll-off in the receptor potential at low frequencies of sinusoidal deflections. Corner frequencies predicted from the adaptation time course varied from 2 to 60 Hz. Voltage-gated conductances also contributed. Roll-off of the receptor potential at the high-frequency end may largely reflect input resistance and capacitance. Corner frequencies predicted by estimated membrane time constants varied from 30 to 150 Hz. In type I cells, slower or no adaptation and shorter membrane time constants predict larger response bandwidths. Frequency tuning in vivo will reflect other factors, including the mechanical response of the otolith and otolithic membrane to head movements.

Vestibular and optokinetic function in the normal guinea pig.

Vestibular and optokinetic function was quantitatively studied in the normal guinea pig through investigation of the vestibulo-ocular reflex (VOR), optokinetic nystagmus (OKN), and the visual vestibulo-ocular reflex (VVOR) by means of sinusoidal stimulation with a computer-controlled rate table (VOR and VVOR) or an optokinetic drum. The VOR exhibited high-pass filter characteristics with steady state gain achieved at 0.125 Hz. The maximum gain was 0.55 at a velocity of 60 degrees/s. The VOR was modeled by a transfer function with best fits obtained with an adaptation time constant of 12.5 seconds. The OKN showed low-pass filter characteristics with a decrease in gain for increase in stimulus amplitude. The maximum gain measured was 0.64. A fractional pole model provided a fit of these data. The VVOR exhibited a mean gain of between 0.6 and 0.7 across the stimulus bandwidth and peak velocities. A model based on a linear combination of the actual OKN and VOR gains provided an estimate of the VVOR gain.

The effects of calcium buffering and cyclic AMP on mechano-electrical transduction in turtle auditory hair cells.

1. The effects of intracellular Ca2+ buffering on hair cell mechanotransduction were studied in an intact cochlear epithelium where the endolymphatic and perilymphatic surfaces could be separately perfused with different Ca2+ solutions. 2. The speed and extent of transducer adaptation increased as the concentration in the patch electrode of the Ca2+ buffer BAPTA was lowered. In 0.1 mM BAPTA or less, the transducer adapted almost completely, with a mean time constant of 0.8 ms. 3. For a fixed internal BAPTA concentration, the transducer conductance varied with hair cell location, increasing towards the high-frequency end of the cochlea, and the time constant of adaptation decreased proportionally. At a given cochlear location, hair cells with larger transducer conductances displayed faster adaptation. We suggest that transducer adaptation accounts for a variable high-pass filter observed in the acoustic tuning curve. 4. The effects of perfusion of 50 microM Ca2+ endolymph depended on the BAPTA concentration of the electrode: with 3 mM BAPTA, adaptation was abolished, but in most recordings with 0.01 or 0.1 mM BAPTA, rapid adaptation was retained. The current-displacement curve was also shifted less the lower the intracellular BAPTA concentration. Cells in the high-frequency half of the papilla retained adaptation at a higher BAPTA concentration. 5. Treatment with the cAMP agonist, 8-bromo-cAMP, or with the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine, caused a rightward shift in the current-displacement curve which was independent of the internal BAPTA concentration. 6. We conclude that the free Ca2+ and cyclic nucleotide concentrations of the hair bundle modulate the position of the activation curve of the transducer. The factors which may be important for the correct functioning of adaptation in vivo are discussed.

Logarithmic time course of sensory adaptation in electrosensory afferent nerve fibers in a weakly electric fish.

1. We recorded single unit activity from individual primary electrosensory afferent axons in the posterior branch of the anterior lateral line nerve of gymnotid weakly electric fish, Apteronotus leptorhynchus. We analyzed the responses of P-type (probability-coding) afferent fibers to externally applied amplitude step changes in the quasi-sinusoidal transdermal potential established by the fish's own electric organ discharge (EOD). 2. In response to AM step increases in transdermal potential, the firing rate of P-type afferents exhibited an abrupt increase followed by an initially rapid and subsequently more gradual decay back toward the baseline level. Afferent responses continued to adapt slowly throughout the duration of prolonged step stimuli lasting > 100 s. The time course of sensory adaptation was similar for all units tested. 3. We introduce a new functional form for describing the time course of sensory adaptation in which the change in firing rate delta r decays logarithmically with time: delta r(t) = A/[B In (t) + 1]. This logarithmic form accurately describes the adaptation time course of P-type afferents over five decades in time, from milliseconds to hundreds of seconds, with only two free parameters. Using a nonlinear least-squares fitting technique, we obtained a mean value of the parameter B, which characterizes the adaptation time course, of 0.149 +/- 0.028 (mean +/- SD, n = 49). 4. We compare logarithmic fits with traditional multiexponential and power law forms and demonstrate that the logarithmic form yields a better characterization of P-type afferent responses. This analysis helps explain the variability in previously reported adaptation time constants, which have ranged from 0.2 to 3.4 s, in gymnotid P-type afferents. 5. We tested the linearity of P-type afferent responses using positive and negative AM steps of varying amplitudes. Aside from nonlinearities associated with rectification (firing rates cannot be negative) and saturation (firing rates cannot exceed the EOD frequency), we found that P-type afferent responses scaled linearly with stimulus amplitude. 6. Based on the observed linearity, we predict the frequency domain response characteristics of P-type afferents and find that the predicted gain and phase are in good agreement with experimental measurements using sinusoidal AM stimuli over a range of AM frequencies from 1 to 100 Hz. Thus the logarithmic parameterization of the step appears to accurately capture the response dynamics of P-type afferents over a wide range of behaviorally relevant AM frequencies. 7. We conclude that the temporal filtering properties of pyramidal cells in the medullary electrosensory nucleus, the electrosensory lateral line lobe (ELL), need to be reevaluated in light of the logarithmic adaptation time course in the periphery, and we discuss implications for the role of P-type afferents in driving a feedback gain control mechanism that regulated ELL pyramidal cell responsiveness.

Analog VLSI architectures for motion processing: from fundamental limits to system applications

This paper discusses some of the fundamental issues in the design of highly parallel, dense, low-power motion sensors in analog VLSI. Since photoreceptor circuits are an integral part of all visual motion sensors, we discuss how the sizing of photosensitive areas can affect the performance of such systems. We review the classic gradient and correlation algorithms and give a survey of analog motion-sensing architectures inspired by them. We calculate how the measurable speed range scales with signal-to-noise ratio (SNR) for a classic Reichardt sensor with a fixed time constant. We show how this speed range may be improved using a nonlinear filter with an adaptive time constant, constructed out of a diode and a capacitor, and present data from a velocity sensor based on such a filter. Finally, we describe how arrays of such velocity sensors call be employed to compute the heading direction of a moving subject and to estimate the time-to-contact between the sensor and a moving object.

Cholinergic modulation of cortical oscillatory dynamics.

1. The effect of cholinergic modulation on cortical oscillatory dynamics was studied in a computational model of the piriform (olfactory) cortex. The model included the cholinergic suppression of neuronal adaptation, the cholinergic suppression of intrinsic fiber synaptic transmission, the cholinergic enhancement of interneuron activity, and the cholinergic suppression of inhibitory synaptic transmission. 2. Electroencephalographic (EEG) recordings and field potential recordings from the piriform cortex were modeled with a simplified network in which cortical pyramidal cells were represented by excitatory input/output functions with gain parameters dependent on previous activity. The model incorporated distributed excitatory afferent input and excitatory connections between units. In addition, the model contained two sets of inhibitory units mediating inhibition with different time constants and different reversal potentials. This model can match effectively the patterns of cortical EEG and field potentials, showing oscillatory dynamics in both the gamma (30-80 Hz) and theta (3-10 Hz) frequency range. 3. Cholinergic suppression of neuronal adaptation was modeled by reducing the change in gain associated with previous activity. This caused an increased number of oscillations within the network in response to shock stimulation of the lateral olfactory tract, effectively replicating the effect of carbachol on the field potential response in physiological experiments. 4. Cholinergic suppression of intrinsic excitatory synaptic transmission decreased the prominence of gamma oscillations within the network, allowing theta oscillations to predominate. Coupled with the cholinergic suppression of neuronal adaptation, this caused the network to shift from a nonoscillatory state into an oscillatory state of predominant theta oscillations. This replicates the longer term effect of carbachol in experimental preparations on the EEG potential recorded from the cortex in vivo and from brain-slice preparations of the hippocampus in vitro. Analysis of the model suggests that these oscillations depend upon the time constant of neuronal adaptation rather than the time constant of inhibition or the activity of bursting neurons. 5. Cholinergic modulation may be involved in switching the dynamics of this cortical region between those appropriate for learning and those appropriate for recall. During recall, the spread of activity along intrinsic excitatory connections allows associative memory function, whereas neuronal adaptation prevents the spread of activity between different patterns. During learning, the recall of previously stored patterns is prevented by suppression of intrinsic excitatory connections, whereas the response to the new patterns is enhanced by suppression of neuronal adaptation.

Galvanic vestibular stimulation for analysis of postural adaptation and stability

Human postural dynamics was investigated in 12 normal subjects by means of a force platform recording body sway, induced by bipolar transmastoid galvanic stimulation of the vestibular nerve and labyrinth. The model adopted was that of an inverted segmented pendulum, the dynamics of postural control being assumed to be reflected in the stabilizing forces actuated by the feet as a result of complex muscular activity subject to state feedback of body sway and position. Time-series analysis demonstrates that a transfer function from stimulus to sway-force response with specific parameters can be identified. In addition, adaptation to the vestibular stimulus is demonstrated to exist, and we describe this phenomenon using quantification in terms of a postural adaptation time constant in the range of 40-50 s. The results suggest means to evaluate adaptive behavior and postural control in the erect human being which may be useful in the rehabilitation of individuals striving to regain upright stance.

Descending input from the vestibulolateral cerebellum suppresses electrosensory responses in the dorsal octavolateralis nucleus of the elasmobranch, Raja erinacea

1. The dorsal octavolateralis nucleus is the primary electrosensory nucleus in elasmobranchs and receives a major descending input from the dorsal granular ridge (DGR), a part of the vestibulolateral cerebellum. Removal of DGR altered the response properties of ascending efferent neurons (AENs), the projection neurons of the dorsal octavolateralis nucleus. 2. Elimination of DGR by lesion or lidocaine microinjection increased the excitability in AENs. Spontaneous activity increased by 680% and receptive fields became 1300% larger. The sensitivity of AENs to electric field stimuli increased by 560% and the time constant of adaptation increased by 300%, while threshold sensitivity remained unchanged. 3. Some electrosensory units responded to proprioceptive stimuli. In intact animals, the spontaneous activity of AENs was much less modulated by changes in fin position than primary electroreceptor afferents. Lesions to DGR appeared to increase the responsiveness of AENs to changes in fin position. 4. These results indicate that the action of DGR on the dorsal octavolateralis nucleus is primarily inhibitory and may function in a gain control mechanism. The possibility also exists for a mechanical-reafferent reduction mechanism in the electrosensory system of the elasmobranch that may be mediated by DGR.

Computational Aspects of the Respiratory Pattern Generator

To help evaluate the hypothesis that the central respiratory rhythm is generated by a network of interacting neurons, a network model of respiratory rhythmogenesis is formulated and examined computationally. The neural elements of the network are driven by tonic inputs and generate a continuous variable representing firing rate. Each neural element in the model can be described by an activation time constant, an adaptation time constant, and a step nonlinearity. Initial network connectivity was based on an earlier proposed model of the central respiratory pattern generator. These connections were adjusted interactively until the model trajectories resembled those observed electrophysiologically. The properties of the resulting network were examined computationally by simulation, determination of the phase resetting behavior of the network oscillator, and examination of the localized eigenstructure of the network. These results demonstrate that the network model can account for a number of diverse physiological observations, and, thus, support the network hypothesis of respiratory rhymogenesis.

Charybdotoxin and apamin sensitivity of the calcium-dependent repolarization and the afterhyperpolarization in neostriatal neurons.

1. Intracellular recordings from neostriatal neurons in an in vitro slice preparation of the rat brain were used to analyze the pharmacological sensitivity of the action potential (AP) repolarization and the afterhyperpolarization (AHP) that follows a single action potential. The interspike voltage trajectory and the AHP could be divided into two main parts: a fast component lasting a few milliseconds and better observed during a train of spikes, and a slow component lasting approximately 250 ms and that comprises the main portion of the AHP. In some cells, a slow (up to 1 s) component of low amplitude was also detected. 2. Single APs were elicited at two imposed membrane potentials (around -60 and around -80 mV). The AP amplitude was larger, the repolarization rate was faster, and the duration was shorter when spikes were evoked at -80 mV. When measured from the -60 mV holding potential, the afterpotential was an AHP with peak amplitude of -5 mV. The afterpotential became a delayed depolarization (DD) at -80 mV. 3. Firing frequency adaptation was voltage sensitive. The firing of APs induced by long intracellular current pulses from a holding potential of -80 mV exhibited only a slow-frequency adaptation (time constant of seconds). However, at -60 mV, an initial and faster frequency adaptation was evident (time constant of tens of milliseconds). 4. The Ca2+ channel blocker Cd2+ retarded AP repolarization rate. This effect correlated with a significant block of the fast and slow components of the AHP. In contrast, Ni2+ had no significant effects on the same parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Fitting Adaptation Models to Velocity Step Responses: Simulation of Normal and Abnormal Responses

A method is described to obtain suitable parameter values for an adaptation model that can be used to simulate velocity step (VS) responses. The input parameters are the dominant time constant fitted to the first part of the VS response and the time of reversal in nystagmus direction. This method allows a particular solution for the model previously defined by others with a vestibulo-ocular reflex (VOR) time constant, a time constant of adaptation, and a fixed (unitary) gain of the adaptation element. However, because it might be arbitrary to assume a unitary gain, we also studied a more general model with a variable gain element. It appeared that patients showing short responses had a short VOR time constant and less adaptation than normal. Patients exhibiting prolonged responses appeared to have an excessively long VOR time constant and more adaptation than normal, presumably to compensate for the long time constant.

Time course of adaptation and recovery from adaptation in the cat auditory-nerve neurophonic

The auditory-nerve neurophonic (ANN) reflects the ensemble response of phase-locked firing in single auditory-nerve fibers to sustained signals. Consequently, neural response properties such as adaptation and recovery from adaptation can be observed. In this study, ANN responses to 800-Hz, 100-ms tones presented at 10-30-dB SL were recorded using bipolar platinum-iridium electrodes placed on the auditory nerve of the cat. The cat ANN adaptation properties were determined and fit to the equation: A(tp) = Yre(-tp/tau Ar) + Yse(-tp/tau As) + Ass. The rapid time constant of adaptation (tau Ar) was invariant across stimulus level, with a mean value of 4.8 (+/- 2.1) ms. The short-term time constant (tau As) decreased approximately 21 ms for each 10-dB increase in probe amplitude. The mean tau As was 116 ms at 10 dB SL, 83.2 ms at 20 dB SL, and 73.5 ms at 30 dB SL. The ANN recovery from adaptation data was analyzed and fit to the equation: A(delta t) = Amax - Yre(-delta t/tau Rr) - Yse(-delta t/tau Rs). Here, tau Rr, the rapid time constant of recovery, and tau Rs, the short-term time constant, were independent of masker intensity in the studied range, with values of 16.2(+/- 9.8) and 125(+/- 50.1) ms, respectively. The results of this study indicate that ANN time constants are comparable to those measured for single units and that the adaptation behavior of phase-locked and nonphase-locked activity appears to be similar.

The responses of cochlear hair cells to tonic displacements of the sensory hair bundle

Hair bundle displacements and receptor potentials were recorded from outer hair cells (OHCs) in organotypic cultures of the mouse cochlea during force steps applied to the bundles with a silica probe of known stiffness. The receptor potentials of some OHCs adapt for excitatory displacements and the time constants of receptor potential adaptation and hair bundle force relaxation for excitatory displacements are very similar. Thus in these OHCs, the receptor potentials correspond to the applied force for excitatory displacements. For inhibitory displacements, the receptor potentials correspond to hair bundle displacement. Some OHC receptor potentials are nonadapting and follow displacement in both the excitatory and inhibitory directions. The hair bundles of nonadapting OHCs are less stiff than those of adapting OHCs and nonadapting OHCs are an order of magnitude less sensitive to hair bundle displacement than adapting OHCs. In response to a combination of excitatory, tonic, hair bundle displacement and current injection, the receptor potentials of nonadapting OHCs decline as the membrane potential is made more positive and reverse near 0 mV. When the receptor potentials of adapting OHCs measured during current injection are compensated for constant input resistance and driving voltage across the transducer conductance, the receptor potential amplitude at the offset of the step displacement is independent of the level and polarity of the injected current. Before adaptation, at the onset of the step displacement of the hair bundle, the amplitude of the receptor potential increases as the injected current becomes more positive. For adapting OHCs, the receptor potential amplitude is a linear function of excitatory bundle displacement for amplitudes less than 50 nm. With negative, but not positive, current injection the receptor potentials at the onset of the displacement tend to saturate and the slope of the function decreases. This voltage dependent control of OHC transducer operating range is proposed to have a role in regulating the sensitivity of the cochlea.

Adaptive Fourier estimation of time-varying evoked potentials.

An estimation procedure for dealing with time-varying evoked potentials is presented here. The evoked response is modeled as a dynamic Fourier series and the Fourier coefficients are estimated adaptively by the least mean square algorithm. Approximate expressions have been developed for the estimation error and time constant of adaptation. A procedure for optimizing the estimator performance is also presented. The effectiveness of the estimator in dealing with simulated as well as actual evoked responses is demonstrated.

GABAergic inhibition shapes temporal and spatial response properties of pyramidal cells in the electrosensory lateral line lobe of gymnotiform fish.

1. The amplitude-coding pyramidal neurons of the first-order nucleus in weakly electric gymnotiform fish (Eigenmannia), the electrosensory lateral line lobe (ELL), exhibit 2 major physiological transformations of primary afferent input. Pyramidal cells rapidly adapt to a step change in amplitude, and they have a center/surround receptive-field organization. This study examined the physiological role of GABAergic inhibition on pyramidal cells. GABAergic synapses onto the somata of pyramidal cells primarily originate from granule-cell interneurons along with descending input. 2. Pyramidal cells fall into two physiologically distinct categories: E units, which are excited by a rise in stimulus amplitude, and I units, which are inhibited by a rise in stimulus amplitude. Microiontophoretic application of bicuculline methiodide onto both types of pyramidal cells increased the time constant of adaptation, defined as the time required for the neuron's response to decay to 37% of its maximum value, by 70-90%. The peak firing rate of E units to a step increase in stimulus amplitude increased by 49%, while the firing rate of I units did not change significantly. 3. Bicuculline application demonstrated that GABAergic inhibition may contribute to the strict segregation of E and I response properties. In the presence of bicuculline, many E units (normally excited only by stimulus amplitude increases) became excited by both increases and decreases; many I units (normally excited only by amplitude decreases) also became excited to increases. 4. The size of the excitatory receptive-field of E units was not affected by bicuculline, although response magnitude increased. The inhibitory surround increased in spatial extent by 175% with bicuculline administration. Neither the size of the I unit receptive-field center nor the response magnitude changed in the presence of bicuculline. The antagonistic surround of I units, however, increased by 49%. 5. The anatomy of the ELL is well understood (see Carr and Maler 1986). The physiological results obtained in this study, along with the results of Bastian (1986a, b), further our understanding of the functional role of the ELL circuitry. Our results suggest that spatial and temporal response properties of pyramidal cells are regulated by different but interacting inhibitory interneurons, some of which use GABA as a neurotransmitter. The activity of these interneurons is in turn controlled by descending feedback systems.

Time constants of the vestibular thermal reaction.

For the thermal test, adaptation time constants of about 100 s are described in the literature. By automatically alternating hot-cold irrigation, as designed by us, precision of stimulus application of different temperatures was considerably improved. Furthermore, temperature was registered with a thermocouple device. The actually effective thermal stimulus on the horizontal canal was calculated by a mathematical model. Nystagmus analysis was carried out automatically with the Kiel-program. With 15 radical cavities (where stimulus intensity is very strong) non-linearities were especially distinct. After switching to the 44 degrees C stimulus, there was an extremely steep rise in the reaction in the form of a so-called "on-effect" or "post-inhibitory overshoot". After reaching maxima of up to 150 degrees/s, the reaction decreased quickly with time constants of 22-45 s.

Cone adaptation in age-related maculopathy.

Cone adaptation was measured in patients with age-related maculopathy (ARM) and age-matched controls. A red stimulus was used to selectively bias responses toward cone function and adaptation was measured 5, 10, 20, and 40 degrees eccentric to fixation. The ARM patients' thresholds were elevated by 1 log unit at 5 and 10 degrees, with the threshold difference reducing to 0.5 log units at 40 degrees. Curves of the form log (threshold luminance) = ae-bt + c (where t is time and a, b, and c are constants) were fitted to each adaptation curve; a procedure involving differentiation of the above equation was used to estimate the constant parameters. Time constants of cone recovery (1/b) were derived for each fitted curve. No significant difference was found between the time constants of the two test groups. Our data suggest that cone adaptation is significantly affected in patients with ARM, with raised cone thresholds occurring for areas well into the peripheral retina. We suggest that the effect is mediated by a reduction in the number of functional cones, which elevates the final cone thresholds without altering the adaptation time constant. Our findings imply that age-related "maculopathy" may not be confined to the macular area, and that early signs of the degeneration may be present in the peripheral retina even when central acuity is normal.