Matthew R. Peterson

ENHANCED LEARNING OF PROPORTIONAL MATH THROUGH MUSIC TRAINING AND SPATIAL-TEMPORAL TRAINING

It was predicted, based on a mathematical model of the cortex, that early music training would enhance spatial-temporal reasoning. We have demonstrated that preschool children given six months of piano keyboard lessons improved dramatically on spatial-temporal reasoning while children in appropriate control groups did not improve. It was then predicted that the enhanced spatial-temporal reasoning from piano keyboard training could lead to enhanced learning of specific math concepts, in particular proportional math, which is notoriously difficult to teach using the usual language-analytic methods. We report here the development of Spatial-Temporal Math Video Game software designed to teach fractions and proportional math, and its strikingly successful use in a study involving 237 second-grade children (age range six years eight months-eight years five months). Furthermore, as predicted, children given piano keyboard training along with the Math Video Game training scored significantly higher on proportional math and fractions than children given a control training along with the Math Video Game. These results were readily measured using the companion Math Video Game Evaluation Program. The training time necessary for children on the Math Video Game is very short, and they rapidly reach a high level of performance. This suggests that, as predicted, we are tapping into fundamental cortical processes of spatial-temporal reasoning. This spatial-temporal approach is easily generalized to teach other math and science concepts in a complementary manner to traditional language-analytic methods, and at a younger age. The neural mechanisms involved in thinking through fractions and proportional math during training with the Math Video Game might be investigated in EEG coherence studies along with priming by specific music.

High-resolution neurometabolic coupling revealed by focal activation of visual neurons

Functional magnetic resonance imaging is an important tool for measuring brain function noninvasively, but the vascular and metabolic changes on which its measurements are based are not fully understood. Here, we examined the relationship between these changes and neural activity on a fine spatial scale through simultaneous measurements of tissue oxygen and extracellular neural activity in the cat lateral geniculate nucleus. Our findings indicate that activity-dependent increases in cerebral blood flow and oxidative metabolism occur on different spatial scales, and that the ratio between the two depends on the size of the activated neural population.

Loss of MeCP2 From Forebrain Excitatory Neurons Leads to Cortical Hyperexcitation and Seizures

Mutations of MECP2 cause Rett syndrome (RTT), a neurodevelopmental disorder leading to loss of motor and cognitive functions, impaired social interactions, and seizure at young ages. Defects of neuronal circuit development and function are thought to be responsible for the symptoms of RTT. The majority of RTT patients show recurrent seizures, indicating that neuronal hyperexcitation is a common feature of RTT. However, mechanisms underlying hyperexcitation in RTT are poorly understood. Here we show that deletion of Mecp2 from cortical excitatory neurons but not forebrain inhibitory neurons in the mouse leads to spontaneous seizures. Selective deletion of Mecp2 from excitatory but not inhibitory neurons in the forebrain reduces GABAergic transmission in layer 5 pyramidal neurons in the prefrontal and somatosensory cortices. Loss of MeCP2 from cortical excitatory neurons reduces the number of GABAergic synapses in the cortex, and enhances the excitability of layer 5 pyramidal neurons. Using single-cell deletion of Mecp2 in layer 2/3 pyramidal neurons, we show that GABAergic transmission is reduced in neurons without MeCP2, but is normal in neighboring neurons with MeCP2. Together, these results suggest that MeCP2 in cortical excitatory neurons plays a critical role in the regulation of GABAergic transmission and cortical excitability.

The Derivation of Direction Selectivity in the Striate Cortex

In the central visual pathway of binocular animals, the property of directional selectivity (DS) is first exhibited in striate cortex. In this study, we sought to determine the neural circuitry underlying the transformation from non-DS neurons to DS cortical cells. In a well established model, DS receptive fields (RFs) are derived from the sum of two non-DS inputs with 90° (quadrature) spatiotemporal phase differences. We explored possible input sources for this model, which include non-DS simple cells and lateral geniculate nucleus (LGN) neurons, by examination of spatiotemporal RFs of single cells and of pairs of cells. We find that distributions of non-DS simple RFs do not match the temporal predictions of the quadrature model because of a lack of long-latency responses. The long-latency inputs could potentially arise from lagged LGN afferents. However, analysis of cell pairs indicates that DS cells receive cortical input from non-DS simple cells for both short- and long-latency components, with temporal phase differences typically <90°. Furthermore, the distribution of minimum phase differences needed to generate DS cells overlaps that exhibited by non-DS simple cells. Considered together, these results are consistent with a linear model whereby DS simple cells are formed from simple-cell inputs, with temporal phase differences often less than quadrature.

Separate Spatial Scales Determine Neural Activity-Dependent Changes in Tissue Oxygen within Central Visual Pathways

The relationship between oxygen levels and neural activity in the brain is fundamental to functional neuroimaging techniques. We have examined this relationship on a fine spatial scale in the lateral geniculate nucleus (LGN) and visual cortex of the cat using a microelectrode sensor that provides simultaneous colocalized measurements of oxygen partial pressure in tissue (tissue oxygen) and multiunit neural activity. In previous work with this sensor, we found that changes in tissue oxygen depend strongly on the location and spatial extent of neural activation. Specifically, focal neural activity near the microelectrode elicited decreases in tissue oxygen, whereas spatially extended activation, outside the field of view of our sensor, yielded mainly increases. In the current study, we report an expanded set of measurements to quantify the spatiotemporal relationship between neural responses and changes in tissue oxygen. For the purpose of data analysis, we develop a quantitative model that assumes that changes in tissue oxygen are composed of two response components (one positive and one negative) with magnitudes determined by neural activity on separate spatial scales. Our measurements from visual cortex and the LGN are consistent with this model and suggest that the positive response spreads over a distance of 1–2 mm, whereas the negative component is confined to a few hundred micrometers. These results are directly relevant to the mechanisms that generate functional brain imaging signals and place limits on their spatial properties.

Neural and perceptual adjustments to dim light

At reduced luminance levels, the visual system integrates light over extended periods of time. Although the general effects of this process are known, specific changes in the visual cortex have not been identified. We have studied the physiological changes that occur during a transition from high to low luminance by measurements of single neurons in the cats primary visual cortex. Under low-luminance conditions, we find increased latencies, expanded temporal responses, and a loss of temporal structure. This results in temporal-frequency tuning curves that are peaked at relatively low frequencies. To examine parallel perceptual changes, we compared perceived temporal frequency in human subjects under high- and low-luminance conditions. Low-luminance flickering patterns are perceived to modulate at relatively high rates. This occurs even though peak sensitivity is shifted to relatively low temporal frequencies. To explore further the perceptual component, we measured perceived temporal frequency in human subjects with unilateral optic neuritis for whom optic nerve transmission is known to be relatively slow and generally similar to the normal physiological state under low luminance. These subjects also perceive relatively high modulation rates through their affected eye. Considered together, these results demonstrate an inverse relationship between the physiological and the perceptual consequences of reduced stimulus luminance. This relationship may be accounted for by shifts of neuronal population responses between high- and low-luminance levels.