Population interactions between parietal and primary motor cortices during reach.

Neural interactions between parietal area 2/5 and primary motor cortex (M1) were examined to determine the timing and behavioral correlates of cortico-cortical interactions. Neural activity in areas 2/5 and M1 was simultaneously recorded with 96-channel microelectrode arrays in three rhesus monkeys performing a center-out reach task. We introduce a new method to reveal parietal-motor interactions at a population level using partial spike-field coherence (PSFC) between ensembles of neurons in one area and a local field potential (LFP) in another. PSFC reflects the extent of phase locking between spike times and LFP, after removing the coherence between LFPs in the two areas. Spectral analysis of M1 LFP revealed three bands: low, medium, and high, differing in power between movement preparation and performance. We focus on PSFC in the 1-10 Hz band, in which coherence was strongest. PSFC was also present in the 10-40 Hz band during movement preparation in many channels but generally nonsignificant in the 60-200 Hz band. Ensemble PSFC revealed stronger interactions than single cell-LFP pairings. PSFC of area 2/5 ensembles with M1 LFP typically rose around movement onset and peaked ∼500 ms afterward. PSFC was typically stronger for subsets of area 2/5 neurons and M1 LFPs with similar directional bias than for those with opposite bias, indicating that area 2/5 contributes movement direction information. Together with linear prediction of M1 LFP by area 2/5 spiking, the ensemble-LFP pairing approach reveals interactions missed by single neuron-LFP pairing, demonstrating that cortico-cortical communication can be more readily observed at the ensemble level.

Characterization of trial-to-trial fluctuations in local field potentials recorded in cerebral cortex of awake behaving macaque.

In analyzing neurophysiologic data, individual experimental trials are usually assumed to be statistically independent. However, many studies employing functional imaging and electrophysiology have shown that brain activity during behavioral tasks includes temporally correlated trial-to-trial fluctuations. This could lead to spurious results in statistical significance tests used to compare data from different interleaved behavioral conditions presented throughout an experiment. We characterize trial-to-trial fluctuations in local field potentials recorded from the frontal cortex of a macaque monkey performing an oculomotor delayed response task. Our analysis identifies slow fluctuations (<0.1 Hz) of spectral power in 22/27 recording sessions. These trial-to-trial fluctuations are non-Gaussian, and call into question the statistical utility of standard trial shuffling. We compare our results with evidence for slow fluctuations in human functional imaging studies and other electrophysiologic studies in nonhuman primates.

Methylphenidate administration to juvenile rats alters brain areas involved in cognition, motivated behaviors, appetite, and stress.

Thousands of children receive methylphenidate (MPH; Ritalin) for attention deficit/hyperactivity disorder (ADHD), yet the long-term neurochemical consequences of MPH treatment are unknown. To mimic clinical Ritalin treatment in children, male rats were injected with MPH (5 mg/kg) or vehicle twice daily from postnatal day 7 (PND7)-PND35. At the end of administration (PND35) or in adulthood (PND135), brain sections from littermate pairs were immunocytochemically labeled for neurotransmitters and cytological markers in 16 regions implicated in MPH effects and/or ADHD etiology. At PND35, the medial prefrontal cortex (mPFC) of rats given MPH showed 55% greater immunoreactivity (-ir) for the catecholamine marker tyrosine hydroxylase (TH), 60% more Nissl-stained cells, and 40% less norepinephrine transporter (NET)-ir density. In hippocampal dentate gyrus, MPH-receiving rats showed a 51% decrease in NET-ir density and a 61% expanded distribution of the new-cell marker PSA-NCAM (polysialylated form of neural cell adhesion molecule). In medial striatum, TH-ir decreased by 21%, and in hypothalamus neuropeptide Y-ir increased by 10% in MPH-exposed rats. At PND135, MPH-exposed rats exhibited decreased anxiety in the elevated plus-maze and a trend for decreased TH-ir in the mPFC. Neither PND35 nor PND135 rats showed major structural differences with MPH exposure. These findings suggest that developmental exposure to high therapeutic doses of MPH has short-term effects on select neurotransmitters in brain regions involved in motivated behaviors, cognition, appetite, and stress. Although the observed neuroanatomical changes largely resolve with time, chronic modulation of young brains with MPH may exert effects on brain neurochemistry that modify some behaviors even in adulthood.