Rebecca K. Harper

Continuous-processing-related event-related potentials in children with attention deficit hyperactivity disorder

Visual information processing in children with attention deficit hyperactivity disorder (ADHD) was studied using event-related potentials recorded during two versions of the Continuous Performance Task (CPT). ADHD children made more errors, and had longer reaction times than normal children on both the single- and dual-target CPT. Event-related potential waveforms were normal in the ADHD children with reference to early processing stages, i.e., contingent negative variation, P1-N1 laterality, and processing negativities, suggesting that ADHD children did not differ in their level of preparedness or their ability to mobilize resources for target identification and categorization. With respect to later processing, P3 amplitude was reduced in the ADHD group, whereas P3 latency was longer than normal. ADHD children had a diminished late frontal negative component, suggestive of reduced involvement in postdecisional processing.

Inspiratory loading elicits aberrant fMRI signal changes in obstructive sleep apnea.

We hypothesized that neural processes mediating deficient sensory and autonomic regulatory mechanisms in obstructive sleep apnea (OSA) would be revealed by responses to inspiratory loading in brain regions regulating sensory and motor control. Functional magnetic resonance imaging (fMRI) signals and physiologic changes were assessed during baseline and inspiratory loading in 7 OSA patients and 11 controls, all male and medication-free. Heart rate increases to inspiratory loading began earlier and load pressures were achieved later in OSA patients. Comparable fMRI changes emerged in multiple brain regions in both groups, including limbic, cerebellar, midbrain, and primary motor cortex. However, in OSA subjects, altered signals appeared in primary sensory thalamus and sensory cortex, supplementary motor cortex, cerebellar cortex and deep nuclei, cingulate, medial temporal, and insular cortices, right hippocampus, and midbrain. Signal delays occurred in basal ganglia. We conclude that areas mediating sensory and autonomic processes, and motor timing, are affected in OSA; many of these areas overlap regions of previously demonstrated gray matter loss.

Event-related potential correlates of linguistic information processing in schizophrenics.

Event-related potentials (ERPs) were recorded from adult schizophrenics and age- and education-matched normal controls during performance of an idiom recognition task involving judgments of the meaningfulness of idiomatic, literal, and nonsense phrases. Schizophrenics produced more errors and had prolonged reaction times while attempting to correctly differentiate meaningful from meaningless phrases. An ERP correlate of that deficit was a larger than normal N400 to idioms and literals, with no difference in N400 amplitude to nonsense phrases. This result was interpreted as evidence that the influence of the linguistic context provided by the first word of two-word idiomatic and literal phrases is reduced in schizophrenia. Schizophrenics also showed reduced amplitude P300.

Development of heart rate dynamics during sleep-waking states in normal infants

ABSTRACT: Previous studies show alterations in the dynamic patterns of cardiac rate in several “at-risk” populations, including apparently healthy infants who subsequently die of the sudden infant death syndrome. In the present study, we examined the maturation of cardiac rate dynamics in normal infants during sleep-waking states over the first 6 mo of life. Instantaneous changes in cardiac R-R intervals were examined in 12-h recordings of 24 normal full-term infants; each infant was recorded at 1 wk and at 1, 2, 3, 4, and 6 mo of age. Scatter plots, consisting of each cardiac R-R interval plotted as a function of the previous interval (Poincaré plots), were constructed for each sleep-waking state in each recording. Analyses of variance were performed on the dispersion of intervals after long and short R-R intervals. In neonates, Poincare plots showed significantly more next-interval dispersion after a long R-R interval than after a short interval, a pattern similar to those observed in older infants and in healthy adults. However, between 1 wk and 1 mo of age, this pattern disappeared and returned gradually beginning at 2 mo of age. The scatter of points in Poincaré plots of infants 1 mo of age approached the patterns of at-risk populations, including infants who subsequently died of the sudden infant death syndrome. These patterns at 1 mo may be indicative of increased vulnerability in normal infants after the neonatal period.

FMRI Responses to Hyperoxia in Congenital Central Hypoventilation Syndrome

Congenital Central Hypoventilation Syndrome (CCHS) patients show partial retention of peripheral chemoreception despite impaired ventilatory responses to CO2 and hypoxia. The condition allows examination of central responses to hyperoxia, which minimizes afferent traffic from peripheral chemoreceptors. We used functional magnetic resonance imaging to assess blood oxygen level–dependent signals over the brain during a baseline and subsequent 2-min hyperoxia (100% O2) period in 14 CCHS and 15 control subjects. After partitioning gray matter and correcting for global effects, the images were analyzed using volume-of-interest time trends followed by repeated-measures ANOVA and conventional cluster analyses. Respiratory rates initially (first 20 s) fell in CCHS, but rose in control subjects; CCHS heart rate increased in the first minute, and then decreased in the second minute, as in controls, but with muted rise and extent of decline. Multiple sites within the cerebellum, midbrain, and pons responded similarly to the challenge in both groups. Response patterns differed early in the right amygdala, paralleling initial respiratory pattern deficits, and late in the right insula, concomitant with cardiac rate differences. Signals also differed between groups in the medial and anterior cingulate, hippocampus, head of caudate, and lentiform nuclei, as well as pontine and midbrain structures and regions within the superior temporal and inferior frontal cortical gyri. The findings emphasize that structures that can alter respiratory timing, such as the amygdala, and modulate sympathetic outflow, such as the right insula, are deficient in CCHS. Medullary and pontine areas targeted by PHOX2B expression are also affected.

Temporal Trends of Cardiac and Respiratory Responses to Ventilatory Challenges in Congenital Central Hypoventilation Syndrome

Congenital central hypoventilation syndrome (CCHS) patients exhibit respiratory deficits to ventilatory challenges, diminished breathing drive during sleep, and reduction of respiratory-related heart rate variation, but at least partially preserved peripheral chemoreception. We hypothesized that integration of afferent activity with respiratory motor output is deficient in CCHS, rather than chemoreceptor failure, and that examination of trends in heart and breathing rates and variabilities following ventilatory challenges may clarify the deficient mechanisms. Twelve children with CCHS and 12 age- and gender-matched control cases were subjected to hyperoxic hypercapnic, poikylocapnic hypoxic, and hyperoxic challenges while supine. Heart and respiratory rates and variabilities during 60-s baseline and 120-s challenge periods were assessed. Hypoxia and hypercapnia enhanced breathing rate in control subjects; in CCHS cases, the rise differed during hypercapnia and did not occur to hypoxia. Hyperoxia showed initial transient patterns in breathing rate that differed between groups. A heart rate increase to hypoxia and late decline to hyperoxia were muted in CCHS patients. In hypercapnia, heart rate followed similar rising patterns in both groups. Overall CCHS heart rate variability was lower in baseline and challenge periods, principally due to diminished respiratory-related variation, especially during hypercapnia. No heart rate variability group differences emerged in hypoxia, and only a late increase for CCHS cases developed in hyperoxia. The findings indicate retention of aspects of chemoreceptor sensitivity in CCHS cases. The heart rate alterations to ventilatory challenges suggest specific compensatory responses of a slower nature remain intact in CCHS, whereas other rapidly changing components are deficient.

Aberrant temporal patterning of slow-wave sleep in siblings of SIDS victims

We assessed the patterning of slow-wave EEG activity during sleep in siblings of sudden infant death syndrome (SIDS) victims over the first 6 months of life. Twelve hour overnight physiologic recordings were obtained from 25 apparently healthy subsequent siblings of SIDS victims and 25 control infants at 1 week, and 1, 2, 3, 4 and 6 months of age. The EEG activity was electronically bandpass filtered, leaving primarily activity ranging from 0.5 to 2.5 Hz (the delta frequency), and the filtered traces were full-wave rectified and integrated over 1 min periods. The recordings were divided into four 3 h segments beginning at sleep onset, and the mean integrated delta activity during quiet sleep was determined for each segment of the night. At 3 and 4 months postnatal age, SIDS siblings displayed increased integrated delta amplitude in the early morning hours relative to control infants. Most SIDS deaths occur in the early morning hours during the 2-4 month age range. We thus speculate that increased delta activity may be indicative of increased arousal thresholds in the early morning, which may contribute to SIDS deaths.

Continuous-processing related ERPS in adult schizophrenia : Continuity with childhood onset schizophrenia

BACKGROUND Previous work with schizophrenic children disclosed deficits on two continuous performance tests (CPTs) and ERP indices of reduced attentional resource allocation. METHODS The two CPTs were administered to adult schizophrenics and matched control subjects. The simple CPT required only that the subject respond whenever the target digit was displayed. The complex version required a response whenever any digit was displayed on two successive trials. Event-related potentials (ERPs) were recorded during task performance. RESULTS Schizophrenics had fewer hits on both CPT versions, showed a greater drop in performance from the simple to the complex CPT, and took longer to respond than controls. The processing negativity (Np) showed a greater amplitude increase from nontarget to target in normals than in schizophrenics, and the overlapping P2 component was more negative in normals. P3 latency was longer in schizophrenics, but P3 amplitude did not differ. CONCLUSIONS Group performance and processing negativity effects replicated those from an earlier study of schizophrenic and normal children administered the same versions of the CPT, suggesting similar abnormalities in the allocation and modulation of information processing resources.

Optical imaging of the ventral medullary surface across sleep-wake states

We hypothesized that spontaneous activity declines over widespread areas of the cat ventral medullary surface (VMS) during rapid eye movement (REM) sleep. We assessed neural and hemodynamic activity, measured as changes in reflected 660- and 560-nm wavelength light, from the VMS during sleep and waking states in five adult, unrestrained cats and in two control cats. Relative to quiet sleep, overall activity declined, and variability, assessed by standard deviation, increased by 25% during REM sleep. Variability in activity during waking also increased by 45% over quiet sleep, but mean activity was unchanged. REM sleep onset was preceded by a reduction in the hemodynamic signal from 5 to 60 s before neural activity decline. The activity decline during REM sleep, previously noted in the goat rostral VMS, extends to intermediate VMS areas of the cat and differs from most neural sites, such as the cortex, hippocampus, and thalamus, which increase activity during REM sleep. The activity decline during REM sleep has the potential to modify VMS responsiveness to baroreceptor and chemoreceptor challenges during the REM state.

Frequency-related, bidirectional limbic responses to cocaine: Comparisons with amphetamine and lidocaine

Dual effects of cocaine on the electrical excitability of limbic structures were investigated by determining current thresholds for afterdischarges (AD) evoked by low and high frequency electrical stimulation. Cocaine, lidocaine and D-amphetamine treatments were compared in order to assess the extent to which cocaines local anesthetic and monoaminergic actions contribute to its effects on limbic afterdischarges. Afterdischarge threshold, duration and propagation for both 3 and 50 Hz stimulation of the amygdala, hippocampus and septal area were tested following saline, cocaine (5 mg/kg), lidocaine (5 mg/kg) and D-amphetamine (2.5-5 mg/kg). Results provide clear evidence that cocaine has a bidirectional effect on hippocampal and amygdalar AD thresholds--significantly increasing sensitivity to low frequency stimulation while significantly decreasing sensitivity to high frequency stimulation at identical brain sites. A frequency-dependent threshold effect also occurred at the septal area. In addition, cocaine reduced limbic AD duration and propagation; these effects proved unrelated to the direction of AD threshold changes. Cocaine effects on afterdischarges differed significantly from those of amphetamine and lidocaine. Comparisons with amphetamine and lidocaine suggest that cocaines local anesthetic action, but not its monoaminergic properties, may contribute to reductions in limbic afterdischarge duration and propagation. However, it is unlikely that either monoaminergic or local anesthetic actions are responsible for cocaines pronounced dual effect on the electrical excitability of major limbic structures. This bidirectional drug effect has interesting neurobiological implications and, in addition, offers a potentially valuable tool for new research on frequency-related functions of the limbic system.