An expanded Transactional Stress and Coping Model for siblings of children with sickle cell disease: family functioning and sibling coping, self-efficacy and perceived social support.

AIM: To investigate the application of an expanded Transactional Stress and Coping Model for the psychological adjustment of non-chronically ill, African-American siblings of children with sickle cell disease (SCD). METHODS: Ninety-seven siblings (M = 11.24 years) from 65 families who care for a child with SCD participated. Primary caregivers completed the Coping Health Inventory for Parents, the Family Relations Scale and the Child Behaviour Checklist, while siblings completed the Kidcope, the Children's Self-Efficacy for Peer Interaction Scale, and the Social Support Scale for Children. RESULTS: Family processes were predictive of sibling adjustment, revealing that family coping, expressiveness and support improved adjustment, while family conflict predicted poor adjustment. CONCLUSION: Findings suggest that family-centered interventions stressing family expressiveness and support, while minimizing conflict, will contribute to sibling psychological adjustment.

On diffusion processes with variable drift rates as models for decision making during learning.

We investigate Ornstein-Uhlenbeck and diffusion processes with variable drift rates as models of evidence accumulation in a visual discrimination task. We derive power-law and exponential drift-rate models and characterize how parameters of these models affect the psychometric function describing performance accuracy as a function of stimulus strength and viewing time. We fit the models to psychophysical data from monkeys learning the task to identify parameters that best capture performance as it improves with training. The most informative parameter was the overall drift rate describing the signal-to-noise ratio of the sensory evidence used to form the decision, which increased steadily with training. In contrast, secondary parameters describing the time course of the drift during motion viewing did not exhibit steady trends. The results indicate that relatively simple versions of the diffusion model can fit behavior over the course of training, thereby giving a quantitative account of learning effects on the underlying decision process.

A site of auditory experience-dependent plasticity in the neural representation of auditory space in the barn owl's inferior colliculus.

The barn owl's optic tectum contains a map of auditory space that is based, in part, on a map of interaural time difference (ITD). Previous studies have shown that this ITD map is shaped by auditory experience. In this study, we investigated whether the plasticity responsible for experience-induced changes in ITD tuning in the tectum occurs within the tectum itself or at an earlier stage in the auditory pathway. We altered auditory experience in young owls by implanting an acoustic filtering device in one ear that caused frequency-dependent changes in sound timing and level. We analyzed the representation of ITD in normal and device-reared owls in two nuclei in the ascending pathway: the external nucleus of the inferior colliculus (ICX), the primary source of ascending auditory input to the tectum, and the lateral shell of the central nucleus of the inferior colliculus (ICCls), the primary source of input to the ICX. In the ICX, device rearing caused adaptive, frequency-dependent changes in ITD tuning, as well as changes in frequency tuning. These changes in tuning were similar to changes that occurred in the optic tectum in the same owls. In contrast, in the ICCls, tuning for ITD and frequency was unaffected by device rearing. The data indicate that plasticity at the level of the ICX is largely responsible for the adaptive adjustments in ITD tuning and frequency tuning that are observed in the optic tecta of owls raised with abnormal auditory experience.

Abnormal auditory experience induces frequency-specific adjustments in unit tuning for binaural localization cues in the optic tectum of juvenile owls.

Early auditory experience shapes the auditory spatial tuning of neurons in the barn owl's optic tectum in a frequency-dependent manner. We examined the basis for this adaptive plasticity in terms of changes in tuning for frequency-specific interaural time differences (ITDs) and level differences (ILDs), the dominant sound localization cues. We characterized broadband and narrowband ITD and ILD tuning in normal owls and in owls raised with an acoustic filtering device in one ear that caused frequency-dependent changes in sound timing and level. In normal owls, units were tuned to frequency-specific ITD and ILD values that matched those produced by sound sources located in their visual receptive fields. In contrast, in device-reared owls, ITD tuning at most sites was shifted from normal by approximately 55 microsec toward open-ear leading for 4 kHz stimuli and 15 microsec toward the opposite-ear leading for 8 kHz stimuli, reflecting the acoustic effects of the device. ILD tuning was shifted in the adaptive direction by approximately 3 dB for 4 kHz stimuli and 8 dB for 8 kHz stimuli, but these shifts were substantially smaller than expected based on the acoustic effects of the device. Most sites also exhibited conspicuously abnormal frequency-response functions, including a strong dependence on stimulus ITD and a reduction of normally robust responses to 6 kHz stimuli. The results demonstrate that the response properties of high-order auditory neurons in the optic tectum are adjusted during development to reflect the influence of frequency-specific features of the binaural localization cues experienced by the individual.

Reflex sympathetic dystrophy: complex regional pain syndrome type I in children with mitochondrial disease and maternal inheritance.

OBJECTIVE: Complex regional pain syndrome type I (CRPS-I), previously known as reflex sympathetic dystrophy (RSD), is an idiopathic condition characterised by localised, abnormally intense and prolonged pain, allodynia and autonomic nervous system changes (ie, swelling, skin colour and temperature changes and altered perspiration) that usually appear following a "noxious" trigger such as trauma or surgery. The objective of this report is to demonstrate that children with CRPS-I can have additional dysautonomic conditions secondary to an underlying maternally inherited mitochondrial disease, an association not previously published. METHODS: Medical records of about 500 patients seen by one paediatric metabolic geneticist were reviewed to identify children meeting established CRPS diagnostic criteria. RESULTS: CRPS-I was present in eight children in seven families, each of which also had additional functional/dysautonomic conditions, the most common (> or = 4 cases per condition) being gastrointestinal dysmotility, migraine, cyclic vomiting and chronic fatigue. All seven probands studied met Nijmegen (2002) diagnostic criteria for definite mitochondrial disease on the basis of the clinical signs and symptoms and biochemical analyses. Six of the seven families met our pedigree-based criteria for probable maternal inheritance. CONCLUSION: In one tertiary-care paediatric genetics practice, children meeting the CRPS-I diagnostic criteria frequently had additional autonomic-related conditions secondary to maternally inherited mitochondrial disease, suggesting that mitochondrial DNA sequence variants can predispose children towards the development of CRPS-I and other dysautonomias. CRPS-I should be considered in patients with mitochondrial disease who complain of idiopathic pain. Maternally inherited mitochondrial disease may not be a rare cause of CRPS-I, especially in children who present with other manifestations of dysautonomia.

Representation of a perceptual decision in developing oculomotor commands.

Behaviour often depends on the ability to make categorical judgements about sensory information acquired over time. Such judgements require a comparison of the evidence favouring the alternatives, but how the brain forms these comparisons is unknown. Here we show that in a visual discrimination task, the accumulating balance of sensory evidence favouring one interpretation over another is evident in the neural circuits that generate the behavioural response. We trained monkeys to make a direction judgement about dynamic random-dot motions and to indicate their judgement with an eye movement to a visual target. We interrupted motion viewing with electrical microstimulation of the frontal eye field and analysed the resulting, evoked eye movements for evidence of ongoing activity associated with the oculomotor response. Evoked eye movements deviated in the direction of the monkey's judgement. The magnitude of the deviation depended on motion strength and viewing time. The oculomotor signals responsible for these deviations reflected the accumulated motion information that informed the monkey's choices on the discrimination task. Thus, for this task, decision formation and motor preparation appear to share a common level of neural organization.

A model of dendritic spine Ca2+ concentration exploring possible bases for a sliding synaptic modification threshold.

We used a biophysical model of an isolated dendritic spine to assess quantitatively the impact of changes in spine geometry, Ca2+ buffer concentration, and channel kinetics on Ca2+ dynamics following high-frequency activation of N-methyl-D-aspartate receptors. We found that varying the buffer concentration in the postsynaptic density from 50 to 500 microM can result in an 8-fold difference in the peak Ca2+ concentration following three pulses at 100 Hz. Similarly, varying the spine neck diameter from 0.1 to 0.55 micron can result in a 15-fold difference in the peak Ca2+ concentration. The amplification of peak Ca2+ concentration also depended on temporal summation of N-methyl-D-aspartate-mediated excitatory postsynaptic currents. Variation of the current duration on the order of 100 msec can significantly affect summation at a given stimulation frequency, resulting in a 10-fold difference in the peak Ca2+ concentration at 100 Hz. It is suggested that activity-dependent modifications of these parameters may be important for the regulation of synaptic plasticity in the brain.

Adaptive adjustment of connectivity in the inferior colliculus revealed by focal pharmacological inactivation.

In the midbrain sound localization pathway of the barn owl, a map of auditory space is synthesized in the external nucleus of the inferior colliculus (ICX) and transmitted to the optic tectum. Early auditory experience shapes these maps of auditory space in part by modifying the tuning of the constituent neurons for interaural time difference (ITD), a primary cue for sound-source azimuth. Here we show that these adaptive modifications in ITD tuning correspond to changes in the pattern of connectivity within the inferior colliculus. We raised owls with an acoustic filtering device in one ear that caused frequency-dependent changes in sound timing and level. As reported previously, device rearing shifted the representation of ITD in the ICX and tectum but not in the primary source of input to the ICX, the central nucleus of the inferior colliculus (ICC). We applied the local anesthetic lidocaine (QX-314) iontophoretically in the ICC to inactivate small populations of neurons that represented particular values of frequency and ITD. We measured the effect of this inactivation in the optic tecta of a normal owl and owls raised with the device. In the normal owl, inactivation at a critical site in the ICC eliminated responses in the tectum to the frequency-specific ITD value represented at the site of inactivation in the ICC. The location of this site was consistent with the known pattern of ICC-ICX-tectum connectivity. In the device-reared owls, adaptive changes in the representation of ITD in the tectum corresponded to dramatic and predictable changes in the locations of the critical sites of inactivation in the ICC. Given that the abnormal representation of ITD in the tectum depended on frequency and was likely conveyed directly from the ICX, these results suggest that experience causes large-scale, frequency-specific adjustments in the pattern of connectivity between the ICC and the ICX.

Hearing impairment induces frequency-specific adjustments in auditory spatial tuning in the optic tectum of young owls.

Bimodal, auditory-visual neurons in the optic tectum of the barn owl are sharply tuned for sound source location. The auditory receptive fields (RFs) of these neurons are restricted in space primarily as a consequence of their tuning for interaural time differences and interaural level differences across broad ranges of frequencies. In this study, we examined the extent to which frequency-specific features of early auditory experience shape the auditory spatial tuning of these neurons. We manipulated auditory experience by implanting in one ear canal an acoustic filtering device that altered the timing and level of sound reaching the eardrum in a frequency-dependent fashion. We assessed the auditory spatial tuning at individual tectal sites in normal owls and in owls raised with the filtering device. At each site, we measured a family of auditory RFs using broadband sound and narrowband sounds with different center frequencies both with and without the device in place. In normal owls, the narrowband RFs for a given site all included a common region of space that corresponded with the broadband RF and aligned with the site's visual RF. Acute insertion of the filtering device in normal owls shifted the locations of the narrowband RFs away from the visual RF, the magnitude and direction of the shifts depending on the frequency of the stimulus. In contrast, in owls that were raised wearing the device, narrowband and broadband RFs were aligned with visual RFs so long as the device was in the ear but not after it was removed, indicating that auditory spatial tuning had been adaptively altered by experience with the device. The frequency tuning of tectal neurons in device-reared owls was also altered from normal. The results demonstrate that experience during development adaptively modifies the representation of auditory space in the barn owl's optic tectum in a frequency-dependent manner.

Neural computations that underlie decisions about sensory stimuli.

Decision-making behavior has been studied extensively, but the neurophysiological mechanisms responsible for this remarkable cognitive ability are just beginning to be understood. Here we propose neural computations that can account for the formation of categorical decisions about sensory stimuli by accumulating information over time into a single quantity: the logarithm of the likelihood ratio favoring one alternative over another. We also review electrophysio-logical studies that have identified brain structures that may be involved in computing this sort of decision variable. The ideas presented constitute a framework for understanding how and where perceptual decisions are formed in the brain.