A prefrontal network model operating near steady and oscillatory states links spike desynchronization and synaptic deficits in schizophrenia.

Schizophrenia results in part from a failure of prefrontal networks but we lack full understanding of how disruptions at a synaptic level cause failures at the network level. This is a crucial gap in our understanding because it prevents us from discovering how genetic mutations and environmental risks that alter synaptic function cause prefrontal network to fail in schizophrenia. To address that question, we developed a recurrent spiking network model of prefrontal local circuits that can explain the link between NMDAR synaptic and 0-lag spike synchrony deficits we recently observed in a pharmacological monkey model of prefrontal network failure in schizophrenia.

Blocking NMDAR Disrupts Spike Timing and Decouples Monkey Prefrontal Circuits: Implications for Activity-Dependent Disconnection in Schizophrenia.

We employed multi-electrode array recording to evaluate the influence of NMDA receptors (NMDAR) on spike-timing dynamics in prefrontal networks of monkeys as they performed a cognitive control task measuring specific deficits in schizophrenia. Systemic, periodic administration of an NMDAR antagonist (phencyclidine) reduced the prevalence and strength of synchronous (0-lag) spike correlation in simultaneously recorded neuron pairs. We employed transfer entropy analysis to measure effective connectivity between prefrontal neurons at lags consistent with monosynaptic interactions and found that effective connectivity was persistently reduced following exposure to the NMDAR antagonist.

Mapping of the preferred direction in the motor cortex.

Directional tuning is a basic functional property of cell activity in the motor cortex. Previous work has indicated that cells with similar preferred directions are organized in columns perpendicular to the cortical surface. Here we show that these columns are organized in an orderly fashion in the tangential dimension on the cortical surface.

Large-scale organization of preferred directions in the motor cortex. I. Motor cortical hyperacuity for forward reaching.

We used statistical methods for spherical density estimation to evaluate the distribution of preferred directions of motor cortical cells recorded from monkeys making reaching movements in 3D space. We found that this distribution, although broad enough to represent the entire 3D continuum of reaching directions, exhibited an enrichment for reaching forward from the body and, to a lesser degree, for reaching backward toward the body. The distribution of preferred directions of cells in the motor cortex may have important implications for motor cortical function and for the decoding of arm trajectories from population activity.

Large-scale organization of preferred directions in the motor cortex. II. Analysis of local distributions.

The spatial arrangement of preferred directions (PDs) in the primary motor cortex has revealed evidence for columnar organization and short-range order. We investigated the large-scale properties of this arrangement. We recorded neural activity at sites on a grid covering a large region of the arm area of the motor cortex while monkeys performed a 3D reaching task.

A phenomenological theory of spatially structured local synaptic connectivity.

The structure of local synaptic circuits is the key to understanding cortical function and how neuronal functional modules such as cortical columns are formed. The central problem in deciphering cortical microcircuits is the quantification of synaptic connectivity between neuron pairs. I present a theoretical model that accounts for the axon and dendrite morphologies of pre- and postsynaptic cells and provides the average number of synaptic contacts formed between them as a function of their relative locations in three-dimensional space.

Logarithmic transformation for high-field BOLD fMRI data.

Parametric statistical analyses of BOLD fMRI data often assume that the data are normally distributed, the variance is independent of the mean, and the effects are additive. We evaluated the fulfilment of these conditions on BOLD fMRI data acquired at 4 T from the whole brain while 15 subjects fixated a spot, looked at a geometrical shape, and copied it using a joystick. We performed a detailed analysis of the data to assess (a) their frequency distribution (i.

Spatial reconstruction of trajectories of an array of recording microelectrodes.

We present a method for estimating the locations of sites visited by an array of microelectrodes. The method relies on visualization of tracks made by electrodes coated in a fluorescent dye. These tracks are used to estimate the parameters of a simple geometrical model that generates coordinates for each recording site.

Cerebellar activation during copying geometrical shapes.

We studied functional MRI activation in the cerebellum during copying 9 geometrical shapes (equilateral triangle, isosceles triangle, square, diamond, vertical trapezoid, pentagon, hexagon, circle, and vertical lemniscate). Twenty subjects were imaged during 3 consecutive 45-s periods (rest, visual presentation, and copying). First, there was a positive relation between cerebellar activation and the peak speed of individual movements.

Modular organization of directionally tuned cells in the motor cortex: is there a short-range order?

We investigated the presence of short-range order (<600 microm) in the directional properties of neurons in the motor cortex of the monkey. For that purpose, we developed a quantitative method for the detection of functional cortical modules and used it to examine such potential modules formed by directionally tuned cells. In the functional domain, we labeled each cell by its preferred direction (PD) vector in 3D movement space; in the spatial domain, we used the position of the tip of the recording microelectrode as the cell's coordinate.