Stuart G. Coupland

A comparison of oscillatory potential and pattern electroretinogram measures in diabetic retinopathy

Both basic and clinical electrophysiological investigations have established that the oscillatory potentials (OP) and pattern electroretinogram (PERG) appear to originate from retinal sites that are in proximity. The OPs, subcomponents of the flash ERG, have been shown to reflect disturbances in retinal circulation, and OP amplitude attenuation or loss may be a distinctive feature of diabetic retinopathy. The PERG has been shown to be abnormal in diseases of the optic nerve and ganglion cell body. Thus its relative sensitivity for detection of electroretinal abnormalities in diabetic retinopathy is in question. This study assessed the sensitivity of ERG and OP measures in their detection of abnormalities of electroretinal function in diabetic patients referred to our laboratory. Thirty-five adult Type I patients were studied: 21 with background retinopathy (BR group), 14 with no evidence of background retinopathy (No BR group), and 25 normal control subjects.Monocular OPs were recorded to full-field ganzfeld stimulation at four stimulus intensities. PERGs were obtained from checkerboard pattern reversal stimulation (checksize = 30′ arc). Peak-to-peak amplitude and peak implicit time measures of PERGs and OPs were obtained. Subsequent multivariate analysis demonstrated significant differences between normals and diabetic patients, including diabetics with no clinical evidence of retinopathy. In addition, the OP and PERG implicit times appear to be unaffected while OP and PERG amplitudes were diminished in patients with background retinopathy. Only OP amplitudes were found to be significantly diminished in diabetic patients with no photographic evidence of background retinopathy. The PERGs were normal in these patients. Overall, the OP amplitude measures were more sensitive than PERG measures in detecting abnormalities in patients with no retinal photographic evidence of background retinopathy.

Frequency‐specific maturation of the eighth nerve and brain‐stem auditory pathway: Evidence from derived auditory brain‐stem responses (ABRs)

Previous studies of human auditory development using frequency-specific auditory brain-stem responses (ABRs) have reported that maturation for both peak and interpeak latencies occurs earlier for responses generated by low-frequency stimuli. In two of these studies, low-frequency ABRs presumed to originate from apical locations in the cochlea were likely dominated by activity from higher frequency regions closer to the base. In the present study, the high-pass noise-masking technique was used to generate derived ABRs that represent activity from isolated place specific regions along the basilar membrane. Analysis of auditory brain-stem maturation based on I-V interpeak latency differences with adult means revealed a frequency-specific pattern of development. Developmental changes occurred faster and mature function was attained earlier for ABRs from the mid-center-frequency (CF) derived conditions than from either the highest or lowest CF derived conditions. The differential maturation of mid-CF derived ABRs may reflect the delayed effects of the pattern of development that occurs in the cochlea.

Maturation of the traveling‐wave delay in the human cochlea

The maturation of the traveling-wave delay in the human cochlea was investigated in 227 subjects ranging in age from 29 weeks conceptional age to 49 years by using frequency specific auditory brain-stem responses (ABRs). The derived response technique was applied to ABRs obtained with click stimuli (presented at a fixed level equal to 60-dB sensation level in normal hearing adults) in the presence of high-pass noise masking (slope 96 dB/oct) to obtain frequency specific responses from octave-wide bands. The estimate of traveling-wave delay was obtained by taking the difference between wave I latencies from adjacent derived bands. It was found that the traveling-wave delay between the octave band with center frequency (CF) of 11.3 kHz and that with CF of 5.7 kHz decreased (about 0.4 ms on average) in exponential fashion with age to reach adult values at 3-6 months of age. This decrease was in agreement with reported data in kitten auditory-nerve fibers. The traveling-wave delays between adjacent octave bands with successive lower CF did not change with age.

ERG electrode in pedriatic patients: Comparison of DTL fiber, PVA-gel, and non-corneal skin electrodes

Hard contact lens electrodes have been the type most frequently used in pediatric electroretinogroply but they are not well-tolerated by patients. The Dawson Trick Litzkow fiber electrode is better tolerated but it is fragile and difficult to sterilize. A new electrode made from anomalous polyvinyl alcohol gel is inexpensive, has stable electrical recording properties, and can be discarded after use. Dermal electrodes have been used for electroretinogram recording for some time; however, there are few reports that directly compare their performance against standard contact lens assemblies. We compared the DTL and the polyvinyl gel electrodes in the same group of subjects and investigated their recording characteristics along with non corneal skin electrodes placed on the infraorbital ridge. Signal-averaged electroretinogram were obtained under both scotopic and photopic stimulation conditions and the implicit time and amplitudes of the a- and b-waves were determined. Overall, dermal recordings generally had shorter implicit times and lower amplitudes than with the fiber or gel electrodes. The dermal electrodes were best tolerated and outlasted the corneal in repeated use. Since amplitude characteristics of the dermal electrodes were generally about 50% of that obtained with corneal electrodes, we feel that under standardized conditions they are acceptable for most clinical recording situations in infants and young children.

The relation between head size and auditory brain‐stem response interpeak latency maturation

In developmental populations, duration of auditory brain-stem response (ABR) I-III, III-V, and I-V vary substantially across individuals, particularly among preterm infants. Adult ABR interpeak latency has a strong correlation with brain-stem size and weaker correlation with head size. To determine if head size might contribute to this increased interpeak latency variability among infants, ABR data were normalized based on head circumference. Normalization by head circumference did not reduce interpeak variability. Further analyses revealed a negative correlation between interpeak latency and head circumference that varied as a function of age. Before 42 weeks conceptional age (CA), a significant relation exists between increased head circumference and decreased duration of the III-V and I-V intervals, but not the I-III interval. For infants older than 42 weeks CA, there was a significant relation between increased head circumference and decreased duration for the I-III intervals but not the III-V and I-V intervals. An age-dependent correlation between decreasing interpeak latency and increasing head circumference suggests that improved neural transmission through the auditory nerve and brain-stem pathway offset or even overcompensate for developmental lengthening of the sensory pathway. Also, developmental time constants obtained from nonlinear curve fit analyses were shorter for normalized than non-normalized data, particularly for the I-V interval. Therefore, correction of ABR data for the length of the sensory pathway may be important to estimate accurately maturation rate for developmental populations.

Postischemic therapy with MK-801 (dizocilpine) in a primate model of transient focal brain ischemia

The purpose of this study was to develop a primate model for assessing EEG, behavior and histology, and to test the effect of NMDA receptor blockade in transient focal ischemia. Squirrel monkeys (Saimiri sciureus) under halothane anesthesia were subjected to 110 min of transient focal ischemia (n = 15) by temporary clip occlusion of the MCA. An eight-lead EEG was recorded. Neurobehavioral testing was done in a subgroup of animals (n = 6). Brain temperature (37.5 degrees C) was monitored and controlled to avoid hypothermia or intergroup temperature differences, and blood pressure was regulated to 60 mmHg. The entire brain was subserially sectioned, and 52 standardized coronal sections encompassing the infarct were examined histologically 2 wk after the ischemia. Animals were randomized to receive either (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801) 1 mg/kg of maleate salt or carrier solution, 20 min and again at 12 h after the onset of ischemia. Cingulate and retrosplenial cortex were examined for NMDA-antagonist-induced neuronal necrosis. No reduction, or trend toward reduction of neurobehavioral deficit was seen with MK-801. MCA occulsion reduced EEG power over the ischemic hemisphere. MK-801 appeared to cause brain activation, and globally increased power at several frequencies. MK-801 did not reduce infarction in either neocortex (p > 0.05) or striatum (p > 0.05). No selective neuronal necrosis was seen in the cingulate or retrosplenial cortex. We conclude that MK-801 given 20 min after the onset of transient ischemia offers no significant neuroprotective effect against either neurobehavioral deficit or ischemic infarction in this model of transient focal ischemia. Further experiments in unanesthetized animals are necessary to determine if MK-801-induced necrosis exists in the gyrencephalic brain, but the enhancement of primate brain electrical activity by MK-801 suggests that brain activation occurs in primates as it does in rodents.

Assessment of cisplatin-induced ototoxicity using derived-band ABRs

Ototoxicity is an adverse side effect of numerous therapeutic agents (amino-glycoside antibiotics, blood chelating agents, diuretics and oncologic drugs) used in treatment of both adult and pediatric patients. Recently, there has been increasing interest in using the auditory brainstem response (ABR) to detect both short-term effects of ototoxicity in adults and long-term effects of drug administration on neonates and children. Since click ABRs have relatively poor frequency selectivity they best approximate the pure-tone hearing threshold in the 2000-4000 Hz frequency range. Hearing loss above or below that frequency range can be present without producing significant abnormalities in the ABR waveform parameters. Frequency-specific ABRs can be obtained using the derived response technique. The purpose of this study was to investigate early cisplatin ototoxicity using both the broadband click and derived ABR and to monitor progressive hearing loss with repeated drug trials in 18 patients studied over a 2-year period. ABRs were obtained serially prior to and following intravenous administration of cisplatin. Derived ABRs were found to be more sensitive than broadband click ABR in detecting early high-frequency hearing loss. For click ABRs, the cumulative dosage of cisplatin at age of ABR examination was correlated with hearing loss in only those patients under 3 years of age. No significant correlation was found between cumulative cisplatin dosage when tested and degree of hearing loss in those patients over 3 years of age.

Oscillatory potential changes related to stimulus intensity and light adaptation

The oscillatory potentials (OPs) are a series of subcomponents of the flash ERG which probably originate in the inner plexiform layer of the retina. Abnormal OPs in various forms of retinopathy include central retinal vein occlusion, congenital stationary night blindness, and diabetic retinopathy. We investigated the effects of stimulus intensity and light adaptation on the OP components identified in our laboratory. OPs were recorded from 20 adult eyes to full-field ganzfeld stimulation at four stimulus intensities from 12 to 62cd/m2. Stimulus flashes were superimposed over a steady background luminance in the ganzfeld. Four background luminances were used over a 3-log unit range from mesopic to photopic levels. Peak-to-peak amplitude and peak implicit time measures of the OPs were obtained. Latency-intensity functions were derived for each of the four OP components at each light-adaptation level. These latency-intensity functions revealed similar curve fitting slopes for all OP subcomponents at lower light-adaptation levels. At higher levels of light adaptation the later subcomponents (OP3 and OP4) showed a flattening of the slope of the latency-intensity function. The investigator concludes that this saturation effect is related to an interaction of rod and cone contribution to the OP waveform.

Visual evoked potentials, intracranial pressure and ventricular size in hydrocephalus

Hydrocephalus in the newborn is frequently seen associated with perinatal asphyxia, birth trauma, or intracranial hemorrhage. Hydrocephalus produces enlargement of the cerebral ventricles and raised intracranial pressure secondary to increases in the amount of cerebrospinal fluid. In this study the relationship between the visual evoked potential and ventricular size in infantile hydrocephalus was investigated. Statistical analysis was used to define them and the role of the visual evoked potential in the clinical and structural assessment of infantile hydrocephalus. The results of these investigations demonstrated a significant relationship between ventricular size and evoked potential parameters and confirmed the usefulness of the flash visual evoked potential examination in the assessment of infants with hydrocephalus.

Variability in clinically measured photopic oscillatory potentials

Oscillatory potentials found on the ascending phase of the electroretinogram b-wave probably originate in some element(s) of the inner plexiform layer. As oscillatory potentials are particularly sensitive to changes in retinal, and possibly choroidal, blood flow, they have been used extensively to provide clinical measures of the degree of retinal ischemia during the progression of diabetic retinopathy. Recent studies in our laboratories have disclosed previously unreported significant variability in the photopic oscillatory potentials on repeated measures even in tightly controlled conditions. The amplitude of five recordable light-adapted wavelets exhibited considerable intra- and inter-subject variability. Until further investigation can determine factors affecting standardization of testing, it appears that changes in oscillatory potential implicit times rather than in amplitudes are a better measurement in clinical neurophysiology.