David M. Alexander

The contribution of apolipoprotein E alleles on cognitive performance and dynamic neural activity over six decades

Neuroimaging shows brain-functional differences due to apolipoprotein E (APOE) polymorphisms may exist decades before the increased risk period for Alzheimers disease, but little is known about their effect on cognition and brain function in children and young adults. This study assessed 415 healthy epsilon2 and epsilon4 carriers and matched epsilon3/epsilon3 controls, spanning ages 6-65, on a range of cognitive tests. Subjects were also compared on a new dynamical measure of EEG activity during a visual working memory task using alphabetical stimuli. epsilon4 subjects had better verbal fluency compared to epsilon3, an effect that was strongest in 51-65 year-olds. No epsilon4 deficits in cognition were found. In 6-15 year-olds, there were differences in total spatio-temporal wave activity between epsilon3 and epsilon4 subjects in the theta band, approximately 200ms post-stimulus. Differences in brain function in younger epsilon4 subjects and superior verbal fluency across the entire age range suggest that the APOE epsilon4 allele is an example of antagonistic pleiotropy.

THE IMPACT OF EARLY LIFE STRESS ON PSYCHOPHYSIOLOGICAL, PERSONALITY AND BEHAVIORAL MEASURES IN 740 NON-CLINICAL SUBJECTS

Early Life Stress (ELS) has been associated with a range of adverse outcomes in adults, including abnormalities in electrical brain activity [1], personality dimensions [40], increased vulnerability to substance abuse and depression [14]. The present study seeks to quantify these proposed effects in a large sample of non-clinical subjects. Data for the study was obtained from The Brain Resource International Database (six laboratories: two in USA, two in Europe, two in Australia). This study analyzed scalp electrophysiological data (EEG eyes open, closed and target auditory oddball data) and personality (NEO-FFI), history of addictive substance use and ELS) data that was acquired from 740 healthy volunteers. The ELS measures were collected via a self-report measure and covered a broad range of events from childhood sexual and physical abuse, to first-hand experience of traumatizing accidents and sustained domestic conflict [41]. Analysis of covariance, controlling for age and gender, compared EEG data from subjects exposed to ELS with those who were unexposed. ELS was associated with significantly decreased power across the EEG spectrum. The between group differences were strongest in the eyes closed paradigm, where subjects who experienced ELS showed significantly reduced beta (F1,405=12.37, p=.000), theta (F1,405=20.48, p=.000), alpha (F1,405=9.65, p=.002) and delta power (F1,450=36.22, p=.000). ELS exposed subjects also showed a significantly higher alpha peak frequency (F1,405=6.39, p=.012) in the eyes closed paradigm. Analysis of covariance on ERP components revealed that subjects who experienced ELS had significantly decreased N2 amplitude (F1,405=7.73, p=.006). Analyses of variance conducted on measures of personality revealed that subjects who experienced ELS had significantly higher levels of neuroticism (F1,264=13.39, p=.000) and openness (F1,264=17.11, p=.000), but lower levels of conscientiousness, than controls (F1,264=4.08, p=.044). The number of ELS events experienced was shown to be a significant predictor of scores on the DASS questionnaire [27], which rates subjects on symptoms of depression (F3,688=16.44, p=.000, R2=.07), anxiety (F3,688=14.32, p=.000, R2=.06) and stress (F3,688=20.02, p=.000, R2=.08). Each additional early life stressor was associated with an increase in these scores independent of age, gender and the type of stressor. Furthermore, the number of ELS experiences among smokers was also found to be a positive predictor of the nicotine dependency score (Faegstrom Test For Nicotine Dependence, [19]) (F3,104=10.99, p=.000, R2=.24), independent of age, gender and type of stressor. In conclusion, we highlight the impact of a history of ELS showed significant effects on brain function (EEG and ERP activity), personality dimensions and nicotine dependence.

EEG MARKERS FOR COGNITIVE DECLINE IN ELDERLY SUBJECTS WITH SUBJECTIVE MEMORY COMPLAINTS

New treatments for Alzheimers disease require early detection of cognitive decline. Most studies seeking to identify markers of early cognitive decline have focused on a limited number of measures. We sought to establish the profile of brain function measures which best define early neuropsychological decline. We compared subjects with subjective memory complaints to normative controls on a wide range of EEG derived measures, including a new measure of event-related spatio-temporal waves and biophysical modeling, which derives anatomical and physiological parameters based on subjects EEG measurements. Measures that distinguished the groups were then related to cognitive performance on a variety of learning and executive function tasks. The EEG measures include standard power measures, peak alpha frequency, EEG desynchronization to eyes-opening, and global phase synchrony. The most prominent differences in subjective memory complaint subjects were elevated alpha power and an increased number of spatio-temporal wave events. Higher alpha power and changes in wave activity related most strongly to a decline in verbal memory performance in subjects with subjective memory complaints, and also declines in maze performance and working memory reaction time. Interestingly, higher alpha power and wave activity were correlated with improved performance in reverse digit span in the subjective memory complaint group. The modeling results suggest that differences in the subjective memory complaint subjects were due to a decrease in cortical and thalamic inhibitory gains and slowed dendritic time-constants. The complementary profile that emerges from the variety of measures and analyses points to a nonlinear progression in electrophysiological changes from early neuropsychological decline to late-stage dementia, and electrophysiological changes in subjective memory complaint that vary in their relationships to a range of memory-related tasks.

Mapping of contextual modulation in the population response of primary visual cortex

We review the evidence of long-range contextual modulation in V1. Populations of neurons in V1 are activated by a wide variety of stimuli outside of their classical receptive fields (RF), well beyond their surround region. These effects generally involve extra-RF features with an orientation component. The population mapping of orientation preferences to the upper layers of V1 is well understood, as far as the classical RF properties are concerned, and involves organization into pinwheel-like structures. We introduce a novel hypothesis regarding the organization of V1’s contextual response. We show that RF and extra-RF orientation preferences are mapped in related ways. Orientation pinwheels are the foci of both types of features. The mapping of contextual features onto the orientation pinwheel has a form that recapitulates the organization of the visual field: an iso-orientation patch within the pinwheel also responds to extra-RF stimuli of the same orientation. We hypothesize that the same form of mapping applies to other stimulus properties that are mapped out in V1, such as colour and contrast selectivity. A specific consequence is that fovea-like properties will be mapped in a systematic way to orientation pinwheels. We review the evidence that cytochrome oxidase blobs comprise the foci of this contextual remapping for colour and low contrasts. Neurodynamics and motion in the visual field are argued to play an important role in the shaping and maintenance of this type of mapping in V1.

Spatio-temporal EEG waves in first episode schizophrenia.

OBJECTIVE Schizophrenia is characterized by a deficit in context processing, with physiological correlates of hypofrontality and reduced amplitude P3b event-related potentials. We hypothesized an additional physiological correlate: differences in the spatio-temporal dynamics of cortical activity along the anterior-posterior axis of the scalp. METHODS This study assessed latency topographies of spatio-temporal waves under task conditions that elicit the P3b. EEG was recorded during separate auditory and visual tasks. Event-related spatio-temporal waves were quantified from scalp EEG of subjects with first episode schizophrenia (FES) and matched controls. RESULTS The P3b-related task conditions elicited a peak in spatio-temporal waves in the delta band at a similar latency to the P3b event-related potential. Subjects with FES had fewer episodes of anterior to posterior waves in the 2-4 Hz band compared to controls. Within the FES group, a tendency for fewer episodes of anterior to posterior waves was associated with high Psychomotor Poverty symptom factor scores. CONCLUSIONS Subjects with FES had altered global EEG dynamics along the anterior-posterior axis during task conditions involving context update. SIGNIFICANCE The directional nature of this finding and its association with Psychomotor Poverty suggest this result is related to findings of hypofrontality in schizophrenia.

Generalization of learning by synchronous waves: from perceptual organization to invariant organization

From a few presentations of an object, perceptual systems are able to extract invariant properties such that novel presentations are immediately recognized. This may be enabled by inferring the set of all representations equivalent under certain transformations. We implemented this principle in a neurodynamic model that stores activity patterns representing transformed versions of the same object in a distributed fashion within maps, such that translation across the map corresponds to the relevant transformation. When a pattern on the map is activated, this causes activity to spread out as a wave across the map, activating all the transformed versions represented. Computational studies illustrate the efficacy of the proposed mechanism. The model rapidly learns and successfully recognizes rotated and scaled versions of a visual representation from a few prior presentations. For topographical maps such as primary visual cortex, the mechanism simultaneously represents identity and variation of visual percepts whose features change through time.

First-episode psychosis and direction of wave propagation at 1 Hz in the EEG.

1Brain Resource Company, Sydney, Australia; 2Brain Dynamics Centre, Westmead Millenium Institute and University of Sydney, Sydney, Australia; 3Neuroscience Institute of Schizophrenia and Allied Disorders, Sydney, Australia; 4Early Psychosis Intervention Program, Liverpool Hospital, NSW, Australia; 5Department of Psychiatry, University of Adelaide, SA, Australia; and 6The University of Sydney, Sydney, Australia

Longitudinal increases in gamma-phase synchrony contrasts with progressive gray matter atrophy in first-episode schizophrenia.

Background: Our integrative neuroscience model of fi rst-episode schizophrenia (FES) emphasizes a dysfunction in the coordinated neural activity required for selective attention in the disorder. This study investigated the longitudinal changes in neural connectivity (assessed by means of 40-Hz gamma synchrony) and neuroanatomy [assessed by magnetic resonance imaging (MRI)] exhibited by patients with FES. Method: Twenty-three FES patients underwent an EEG recording in response to an auditory oddball task, both at baseline and 2–3 years subsequently. Gammaphase synchrony was extracted from the EEG signal for L/R frontal, temporal and posterior brain regions. Thirteen of these patients also underwent an MRI scan at baseline and follow-up, and an automated masking procedure was used to calculate the GM volumes of the analogous cortical regions. A 2 ́ 6 (‘time’ ́ ‘region’) repeated-measures ANOVA was used for statistical analysis. Results: An inverse relationship was observed between the longitudinal changes in gamma synchrony and the longitudinal changes in GM volume. While the patients with FES lost signifi cant frontal and parietal GM over the follow-up interval, they also showed a corresponding increase in posterior gamma-phase synchrony. Conclusions: These results indicate that while gammaphase synchrony increases over the initial years of illness in patients with FES, GM volume decreases in corresponding cortical regions. Given the role that gamma-phase synchrony has been proposed to play in the integration of discrete perceptual events, these fi ndings support the idea that schizophrenia is caused by a dysfunction in neural connectivity. Late-onset bipolar disorder: preliminary results from Sydney

10-02 The neurodevelopmental effects of apolipoprotein E alleles on brain function.

336 participants. We detected subtle defi cits in information processing and vigilance in people bearing the lowexpressing genotype. Men with the ‘low’ genotype exhibited additional defi cits in executive function. Conclusions: Study of the genetic contributors to variation in normal brain function will provide insight into normal neurological processes and have direct relevance to our understanding of such disorders as depression, anxiety and Alzheimer’s disease. Because the consequences of individual polymorphisms are generally subtle, an integrative approach that allows for large cohorts is essential to assess their effects.

Fast Fourier transform in the spiral honeycomb image algebra

The Fourier transform is one of the most important transformations in image processing. A major component of this influence comes from the ability to implement it efficiently on a digital computer. This paper describes one such efficient implementation and discusses its implications to digital technology as well as biological vision. The significance of the fast Fourier transform (FFT) presented in this paper is that it provides geometrical meaning to the regrouping of a Cooley-Tukey type FFT.