Biomedical subjects

L B Geffen

Publications and source records attributed to L B Geffen.

At least 19 recordsLinked to original sources

PubMed2005

Genetic covariation between event-related potential (ERP) and behavioral non-ERP measures of working-memory, processing speed, and IQ.

The aim of this study was to identify genetic covariants for fundamental measures of brain function (event-related potentials (ERPs): P300 latency and slow wave amplitude recorded in a working-memory task) and more complex cognitive measures (behavioral non-ERP measures: working-memory performance, information processing speed, IQ). Data were collected from 252 monozygotic and 297 dizygotic twin pairs aged 16. Multivariate modeling identified two independent genetic factors associated with processing speed that also influenced working-memory performance (one reflected the duration of neural activity required to evaluate target information, the other reflected more general cognitive and speed-related abilities). However, the allocation of neural resources, as assessed by ERP slow wave amplitude measures, was not associated with the other cognitive measures investigated. Thus, of the ERP measures examined, P300 latency, but not slow wave amplitude, may be an informative measure to include (i.e., with working-memory performance) in future multivariate linkage and association analyses of cognitive function.

Cognition↗

PubMed2003

Slow binocular rivalry in bipolar disorder.

BACKGROUND: The rate of binocular rivalry has been reported to be slower in subjects with bipolar disorder than in controls when tested with drifting, vertical and horizontal gratings of high spatial frequency. METHOD: Here we assess the rate of binocular rivalry with stationary, vertical and horizontal gratings of low spatial frequency in 30 subjects with bipolar disorder, 30 age- and sex-matched controls, 18 subjects with schizophrenia and 18 subjects with major depression. Along with rivalry rate, the predominance of each of the rivaling images was assessed, as was the distribution of normalized rivalry intervals. RESULTS: The bipolar group demonstrated significantly slower rivalry than the control, schizophrenia and major depression groups. The schizophrenia and major depression groups did not differ significantly from the control group. Predominance values did not differ according to diagnosis and the distribution of normalized rivalry intervals was well described by a gamma function in all groups. CONCLUSIONS: The results provide further evidence that binocular rivalry is slow in bipolar disorder and demonstrate that rivalry predominance and the distribution of normalized rivalry intervals are not abnormal in bipolar disorder. It is also shown by comparison with previous work, that high strength stimuli more effectively distinguish bipolar from control subjects than low strength stimuli. The data on schizophrenia and major depression suggest the need for large-scale specificity trials. Further study is also required to assess genetic and pathophysiological factors as well as the potential effects of state, medication, and clinical and biological subtypes.

Adult↗

PubMed2001

Genetic influence on ERP slow wave measures of working memory.

Individual differences in the variance of event-related potential (ERP) slow wave (SW) measures were examined. SW was recorded at prefrontal and parietal sites during memory and sensory trials of a delayed-response task in 391 adolescent twin pairs. Familial resemblance was identified and there was a strong suggestion of genetic influence. A common genetic factor influencing memory and sensory SW was identified at the prefrontal site (accounting for an estimated 35%-37% of the reliable variance) and at the parietal site (51%-52% of the reliable variance). Remaining reliable variance was influenced by unique environmental factors. Measurement error accounted for 24% to 30% of the total variance of each variable. The results show genetic independence for recording site, but not trial type, and suggest that the genetic factors identified relate more directly to brain structures, as defined by the cognitive functions they support, than to the cognitive networks that link them.

Adolescent↗

PubMed2001

Genetic influence on the variance in P3 amplitude and latency.

The P3(00) event-related potential (ERP) component is widely used as a measure of cognitive functioning and provides a sensitive electrophysiological index of the attentional and working memory demands of a task. This study investigated what proportion of the variance in the amplitude and latency of the P3, elicited in a delayed response working memory task, could be attributed to genetic factors. In 335 adolescent twin pairs and 48 siblings, the amplitude and latency of the P3 were examined at frontal, central, and parietal sites. Additive genetic factors accounted for 48% to 61% of the variance in P3 amplitude. Approximately one-third of the genetic variation at frontal sites was mediated by a common genetic factor that also influenced the genetic variation at parietal and central sites. Familial resemblance in P3 latency was due to genetic influence that accounted for 44% to 50% of the variance. Genetic covariance in P3 latency across sites was substantial, with a large part of the variance found at parietal, central, and frontal sites attributed to a common genetic factor. The findings provide further evidence that the P3 is a promising phenotype of neural activity of the brain and has the potential to be used in linkage and association analysis in the search for quantitative trait loci (QTLs) influencing cognition.

Adolescent↗

PubMed2001

Genetic covariance among measures of information processing speed, working memory, and IQ.

The genetic relationship between lower (information processing speed), intermediate (working memory), and higher levels (complex cognitive processes as indexed by IQ) of mental ability was studied in a classical twin design comprising 166 monozygotic and 190 dizygotic twin pairs. Processing speed was measured by a choice reaction time (RT) task (2-, 4-, and 8-choice), working memory by a visual-spatial delayed response task, and IQ by the Multidimensional Aptitude Battery. Multivariate analysis, adjusted for test-retest reliability, showed the presence of a genetic factor influencing all variables and a genetic factor influencing 4- and 8-choice RTs, working memory, and IQ. There were also genetic factors specific to 8-choice RT, working memory, and IQ. The results confirmed a strong relationship between choice RT and IQ (phenotypic correlations: -0.31 to -0.53 in females, -0.32 to -0.56 in males; genotypic correlations: -0.45 to -0.70) and a weaker but significant association between working memory and IQ (phenotypic: 0.26 in females, 0.13 in males; genotypic: 0.34). A significant part of the genetic variance (43%) in IQ was not related to either choice RT or delayed response performance, and may represent higher order cognitive processes.

Adolescent↗

PubMed2001

The n-back as a dual-task: P300 morphology under divided attention.

The n-back task was hypothesized to be a dual task, permitting the imposition of parametrically increasing attentional and working memory demands, while keeping constant the demands of an embedded matching subtask. Visual targets were presented for 200 ms every 2.2 s at pseudorandomly varying positions on a computer screen. Participants were required to remember the most recent 0, 1, 2, or 3 positions and responded with a choice button push to whether the current target position matched the position presented n items previously. P300 peak latency was constant across n-back tasks, reflecting constant perceptual and cognitive demands of the matching subtask. P300 peak amplitude decreased with increasing memory load, reflecting reallocation of attention and processing capacity away from the matching subtask to working memory activity. These data support a dual-task nature of the n-back, which should be considered when employing this paradigm.

Adult↗

PubMed1999

Concussion in contact sports: reliable change indices of impairment and recovery.

This paper reports a follow-up study to an article on the sensitivity of three tests of speed of information processing to impairment after concussion (Hinton-Bayre, Geffen, & McFarland, 1997). Group analyses showed that practice effects can obscure the effects of concussion on information processing, thereby making the assessment of functional impairment and recovery after injury unreliable. A Reliable Change Index (RCI) was used to assess individual variations following concussion. It was found that 16 of the 20 concussed professional rugby league players were impaired 1-3 days following injury. It was also demonstrated that 7 players still displayed cognitive deficits at 1-2 weeks, before returning to preseason levels at 3-5 weeks. The RCI permits comparisons between different tests, players, and repeated assessments, thereby providing a quantitative basis for decisions regarding return to play.

Adult↗

PubMed1995

Event related potentials during covert orientation of visual attention: effects of cue validity and directionality.

Covert orientation of attention was studied in 30 adults who fixated warning cues and pressed a button at target onset. Directional cues (arrows) indicated the most probable (p = 0.8) side of target occurrence. Subjects responded fastest when validly cued, slowest to invalidly cued targets, and at an intermediate rate when the cue (a cross) was not directional. Directional cues took longer to evaluate (increased N1 and P2 latencies) and produced more focussed attention and greater response preparation (enhanced CNV and P3 amplitude) than non-directional cues. These findings indicate that the expectancy of a target can be manipulated by a spatial cue at three levels, sensory, attention, and response preparation, and lead to changes in the sensory perceptual processing of the target. Validly cued targets produced an increase in P1 amplitude reflecting attention enhanced sensory processing whereas invalidly cued targets increased N1 and P3 amplitudes reflecting the re-orientation of attention, and further processing and updating of information required of low probability stimuli respectively. P3 latency to invalidly cued targets was also delayed reflecting the additional processes required to shift attention to a new location. The P3 latency validity effect was smaller than that found for response time suggesting response execution may also be affected by spatial attention.

Aged↗

PubMed1994

Interhemispheric control of manual motor activity.

The interhemispheric control of manual motor processes is reviewed, focusing on the clinical evidence from patients with commissurotomies and with agenesis of the corpus callosum. There is little evidence for a role of the corpus callosum in transferring explicit motor commands. Rather, the corpus callosum seems important for transferring lateralised information (such as verbal or visuospatial activity) of the pre-motor variety. Also, the corpus callosum may become very significant when movement begins: there appears to be a transcallosal passage of corollary motor signals and feedback sensory signals that are used to control asychronous bimanual movements and to inhibit the opposite hemisphere from interfering when a simple unimanual movement is required.

Attention↗

PubMed1994

Auditory verbal learning test components as measures of the severity of closed-head injury.

Auditory verbal learning and memory was assessed in 18 patients with moderate-severe closed-head injury (CHI). Compared to a matched control group, performance of the CHI subjects on all measures of the Auditory Verbal Learning Test (AVLT) was significantly worse. Discriminant function analysis correctly classified 90% of subjects as CHI or control using the three most reliable measures of the AVLT. Retention of the learning list following the distractor trial varied with severity of injury as indexed by duration of post-traumatic amnesia (PTA). The more severe the injury (longer PTA), the fewer words were recalled after interference (r = -0.72). Susceptibility of verbal memory to retroactive interference is sensitive to the presence and severity of CHI.

Adolescent↗

PubMed1994

Test-retest reliability of a new form of the auditory verbal learning test (AVLT).

The equivalence between the original form (Form 1) of the Auditory Verbal Learning Test (AVLT), and a new form (Form 4) was examined in 51 normal adult subjects (20-67 years) of average estimated intelligence who were assessed in two separate sessions. Performance on the new form was equivalent to that on the original and most measures on the two tests showed significant positive correlations. Test-retest reliability of AVLT scores between sessions was also assessed, both globally and separately for Form 1 followed by Form 4 and for the reverse order. The most reliable measures on the AVLT were the total number of words learned over the five learning trials, (r =.77), and performance on the retention trial of the learning list following the presentation and performance of the distractor list (r =.70). These measures are sufficiently robust for use in clinical serial assessments.

Journal Article↗

PubMed1993

Galanin-containing fibers innervate substance P-containing neurons in the pedunculopontine tegmental nucleus in humans.

Galanin is a putative peptide transmitter distributed widely in the central nervous system. Galanin shows potent inhibitory effects on neuronal activity and learning behaviors induced or mediated by acetylcholine. Here, we demonstrate that in humans there are abundant galanin-containing fibers in the pedunculopontine tegmental nucleus, the lateral dorsal tegmental nucleus and the oral pontine reticular nucleus. These neurons contain both acetylcholine and substance P (SP). Using a double-immunostaining method, we show that galanin-containing terminals from pericellular baskets around many SP-positive neurons in these nuclei. Our results suggest galanin may influence brain functions via inputs to the ascending mesopontine acetylcholine-containing nuclei.

Aged↗

PubMed1993

Loss of C1 and C3 epinephrine-synthesizing neurons in the medulla oblongata in Parkinson's disease.

We used immunohistochemical analysis to determine whether medulla oblongata neurons containing phenylethanolamine N-methyltransferase (PNMT) are affected in patients who died with idiopathic Parkinson's disease (n = 7) compared with age-matched control subjects who died with nonneurological diseases (n = 8). Transverse sections (50 microns) of medulla were prepared either for conventional neuropathological examination or for the immunohistochemical demonstration of PNMT. Immunopositive neurons at approximately 30 rostrocaudal levels, evenly spaced throughout the whole medulla, were mapped and cells in each section were counted with a camera lucida system linked to a computer. In the ventrolateral medulla, from the level of the obex to 11 mm rostral to the obex where the C1 group of neurons is located, there were 7,631 +/- 844 PNMT-positive neurons in control brains and 3,604 +/- 1,051 in brains affected by Parkinson's disease (47% of control). Many PNMT-positive neurons contained Lewy bodies. We observed a previously undescribed midline (C3) group of PNMT-positive neurons in normal brains, and this group was also severely affected (12% of control) in parkinsonian brains. Neither the C2 group nor the small PNMT-positive neurons in the nucleus tractus solitarii were significantly reduced in numbers but there was a reduction in the numbers of melanin-pigmented cells in both the ventrolateral (50% of control) and the dorsomedial (79% of control) region. Our results demonstrate a selective loss of C1 and C3 PNMT-positive neurons, providing the first quantitative evidence for damage to these presumed brainstem sympathetic premotor neurons in Parkinson's disease. These changes may underlie some of the autonomic symptoms occurring in this condition.

Aged↗

PubMed1993

Event-related potentials associated with covert orientation of visual attention in Parkinson's disease.

Event-related potentials (ERPs) were measured in a group of patients with idiopathic Parkinson's disease and compared with a matched control group during a task involving covert orientation of visual attention. Central warning cues directed attention to the probable location of a lateralized signal that required a button-press response. Parkinson patients had enhanced post-cue P1 (at Oz) and P2 (at Cz) amplitudes, delayed N1 (at Oz) latencies, and diminished CNV amplitudes. Post-target amplitudes were similar to controls, except for an enhanced P1 to invalidly cued targets, and delayed N1 and P3 target latencies. These results indicate that Parkinson patients, in addition to their motor deficits, process spatial cues more effortfully and slowly, have impaired response preparation, and process imperative stimuli more slowly.

Aged↗

PubMed1992

Age-related loss of dorsal vagal neurons in Parkinson's disease.

Older patients who die with Parkinson's disease (PD) have fewer pigmented neurons in the locus coeruleus and fewer substance P-containing neurons in mesopontine tegmental nuclei. We analyzed two other medullary nuclei, the dorsal vagal nucleus and the hypoglossal nucleus, in eight PD patients and six normal controls by counting neurons in serial Nissl stained sections to determine the relationship between age at death and cell loss in these nuclei. PD-related neurodegenerative changes (Lewy bodies and neuronal loss) were present only in the dorsal vagal nucleus (13,637 +/- 1,323 neurons in PD, 24,885 +/- 1,157 in normal controls). Cells in the intermediate rostrocaudal part of the nucleus were most severely affected. There was a significant correlation between loss of vagal neurons and age at death in PD patients. No age-related cell loss was present in the dorsal vagal nucleus of normal brains, or in the hypoglossal nucleus in either PD or normal brains. These results confirm that age-related cell death depends on whether or not there is coexistent PD.

Aged↗

PubMed1991

Cytoarchitecture of serotonin-synthesizing neurons in the pontine tegmentum of the human brain.

We have employed immunohistochemical and morphometric procedures to study serotonin-synthesizing (PH8-immunoreactive) neurons in the pontine reticular formation of the adult human. PH8-immunoreactive neurons were found in three cytoarchitectural regions: the median raphe nucleus (MnR), oral pontine reticular nucleus (PnO), and supralemniscal region (group B9). On the basis of cell size, morphology, and position, it was possible to distinguish distinct subgroups within the MnR (dorsal, midline, and paramedian cell clusters) and within the PnO (dorsal and central cell clusters), whereas within the B9 there were no distinct cell clusters. We have estimated that there are approximately 125,000 PH8-immunoreactive neurons in the human pontine tegmentum; 64,400 in the MnR, 30,700 in PnO and 29,000 in B9. The large numbers of serotonin-synthesizing neurons in the human pontine tegmentum contrasts with their relative paucity in nonprimate species such as rats and cats. Nonhuman primates also have large numbers of pontine serotonergic neurons but the morphology of these neurons and their spatial arrangement is significantly different in humans. These results are discussed with respect to the possible projections and functions of these neurons in humans.

Aged↗

PubMed1991

Distribution, morphology and number of monoamine-synthesizing and substance P-containing neurons in the human dorsal raphe nucleus.

The distribution, morphology and number of serotonin-, catecholamine- and substance P-containing neurons in the human dorsal raphe nucleus were studied. Parallel series of sections were prepared from 10 human brainstems obtained at autopsy from patients without neurological disease aged between 42 and 88 years. The neurons were identified using immunohistochemistry with antibodies raised against phenylalanine hydroxylase (tryptophan hydroxylase-containing, serotonin neurons), tyrosine hydroxylase (catecholamine neurons) and substance P. A reference series of Nissl-stained sections was also prepared and data published separately were used to delineate the subnuclear divisions of the dorsal raphe nucleus and to establish the total number of neurons in each subnucleus. The following principal findings emerged. (1) Serotonin-synthesizing neurons are present in all regions of the dorsal raphe nucleus and their total number is 165,000 +/- 34,000. The same types of neurons as those seen in Nissl material characterize each of the five subnuclei (caudal, dorsal, ventral, ventrolateral and interfascicular). (2) Substance P-containing neurons mostly occupy the rostral part of the nucleus and their number is 74,600 +/- 17,600. (3) Catecholamine cells are only found in the rostral part of the dorsal raphe nucleus and their number is 5600 +/- 3400. (4) In the ventral and interfascicular subnuclei the combined number of serotonin-synthesizing and substance P-containing neurons exceeds the total number of Nissl-stained neurons suggesting that serotonin and substance P co-exist in a substantial part of the cell population of the dorsal raphe nucleus. This is further supported by the highly similar morphology and size of these neurons. It is concluded that there are demonstrable chemical differences between the various subregions of the human dorsal raphe nucleus. These differences are in harmony with the results of hodological studies in animals, which have demonstrated differential projection pathways emerging from this nucleus.

Adult↗

PubMed1991

Substance P-containing neurons in the mesopontine tegmentum are severely affected in Parkinson's disease.

Substance P immunoreactive (SP+) neurons were analysed quantitatively in serial sections of the mesopontine tegmentum in 6 patients with idiopathic Parkinson's disease and 5 age-matched normal controls. In the tegmentum of the Parkinson's disease brains many SP+ neurons contained swollen, twisted neuronal processes as well as Lewy bodies. There were significant reductions in the total number of SP+ neurons in the pedunculopontine tegmental nucleus (loss 43%), in the laterodorsal tegmental nucleus (loss 28%), in the oral pontine reticular nucleus (loss 41%) and in the median raphe nucleus (loss 76%). It was the large SP+ (greater than 20 microns) neurons that were particularly affected. In our control group we did not document a significant relationship between age at death and number of SP+ neurons in these tegmental nuclei or between age at death and number of pigmented neurons in the locus coeruleus. In contrast, in patients with Parkinson's disease, there was a strong inverse relationship between age at death and numbers of SP+ and pigmented neurons. Our findings suggest an interaction between the pathophysiological mechanisms initiated by Parkinson's disease and other processes related to ageing. Since tegmental SP+ neurons are affected by the primary pathological processes underlying Parkinson's disease as severely as catecholamine-synthesizing neurons are affected, theories of pathogenesis and therapeutic strategies in Parkinson's disease will need to take into account the involvement of these SP+ neurons.

Aged↗