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Motor functions or sensory stimuli lead to a correlated firing among neurons in the brain cortex that occurs quickly and depends on the nature of stimulus. The distance between two neurons also influences the response behavior, implying the need for an alteration in neural coding models based on single neuron firing rates. Joint peri-stimulus time histograms aid these studies on neuronal interactions.

There is considerable overlap between the cognitive deficits observed in humans with frontal lobe damage and those described in patients with Parkinson's disease. Similar frontal impairments have been found in the 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP) primate model of Parkinsonism. Here we provide quantitative documentation of the cognitive, oculomotor, and skeletomotor dysfunctions of monkeys trained on a frontal task and treated with low-doses (LD) of MPTP. Two rhesus monkeys were trained to perform a spatial delayed-response task with frequent alternations between two behavioral modes (GO and NO-GO). After control recordings, the monkeys were treated with one placebo and successive LD MPTP courses. Monkey C developed motor Parkinsonian signs after a fourth course of medium-dose (MD) MPTP and later was treated with combined dopaminergic therapy (CDoT). There were no gross motor changes after the LD MPTP courses, and the average movement time (MT) did not increase. However, reaction time (RT) increased significantly. Both RT and MT were further increased in the symptomatic state, under CDoT. Self-initiated saccades became hypometric after LD MPTP treatments and their frequency decreased. Visually triggered saccades were affected to a lesser extent by the LD MPTP treatments. All saccadic parameters declined further in the symptomatic state and improved partially during CDoT. The number of GO mode (no-response, location, and early release) errors increased after MPTP treatment. The monkeys made more perseverative errors while switching from the GO to the NO-GO mode. Saccadic eye movement patterns suggest that frontal deficits were involved in most observed errors. CDoT had a differential effect on the behavioral errors. It decreased omission errors but did not improve location errors or perseverative errors. Tyrosine hydroxylase immunohistochemistry showed moderate ( approximately 70-80%) reduction in the number of dopaminergic neurons in the substantia nigra pars compacta after MPTP treatment. These results show that cognitive and motor disorders can be dissociated in the LD MPTP model and that cognitive and oculomotor impairments develop before the onset of skeletal motor symptoms. The behavioral and saccadic deficits probably result from the marked reduction of dopaminergic neurons in the midbrain. We suggest that these behavioral changes result from modified neuronal activity in the frontal cortex.

This paper explores if dynamic modulation of coherent firing serves cortical functions. We recorded neuronal activity in the frontal cortex of behaving monkeys and found that temporal coincidences of spikes firing of different neurons can emerge within a fraction of a second in relation to the animal behavior. The temporal patterns of the correlation could not be predicted from the modulations of the neurons firing rate and finally, the patterns of correlation depend on the distance between neurons. These findings call for a revision of prevailing models of neural coding that solely rely on firing rates. The findings suggest that modification of neuronal interactions can serve as a mechanism by which neurons associate rapidly into a functional group in order to perform a specific computational task. Increased correlation between members of the groups, and decreased or negative correlation with others, enhance the ability to dissociate one group from concurrently activated competing groups. Such modulation of neuronal interactions allows each neuron to become a member of several different groups and participate in different computational tasks.

The study was designed to reveal occurrences of precise firing sequences (PFSs) in cortical activity and to test their behavioral relevance. Two monkeys were trained to perform a delayed-response paradigm and to open puzzle boxes. Extracellular activity was recorded from neurons in premotor and prefrontal areas with an array of six microelectrodes. An algorithm was developed to detect PFSs, defined as a set of three spikes and two intervals with a precision of +/-1 ms repeating significantly more than expected by chance. The expected level of repetition was computed based on the firing rate and the pairwise correlation of the participating units, assuming a Poisson distribution of event counts. Accordingly, the search for PFSs was corrected for rate modulations. PFSs were found in 24/25 recording sessions. Most PFSs (76%) were composed of spikes of more than one unit but usually not more than two units (67%). The PFSs spanned hundreds of milliseconds, and the average interval between two events within the PFSs was 200 ms. No traces of periodic oscillations were found in the PFS intervals. The bins of the matrix that were defined as PFSs were isolated temporally: the spikes that generated PFSs were not associated with high-frequency bursts or rapid coherent rate fluctuations. A given PFS tended to be correlated with the animal's behavior. Furthermore, for 19% of the PFS pairs that shared the same unit composition, each member of the pair was associated with a different type of behavior. The PFSs often appeared in clusters that were associated with particular phases of the behavior. The firing rate of single units did not provide a full explanation for the timing and structure of these clusters. A reduced spike train (RST) was defined for each unit by taking all spikes of that unit that were part of any PFS. In 88% of the cases the degree of modulation of the RST was higher than that of the complete spike train. The results suggest that relevant information is carried by the fine temporal structure of cortical activity. A coding scheme that involves such temporal structures is rich and sufficiently flexible to facilitate a rapid organization of cortical neurons into functional groups. The results can be accounted for by the synfire chain model, which suggests that cortical activity is mediated by synchronous activation of neural groups in a reverberatory mode.

This report describes exploration of the hypothesis that cortical function is mediated by dynamic modulation of coherent firing in groups of neurons. We recorded neuronal activity in the frontal cortex of behaving monkeys and found that correlation between neurons changed frequently within a fraction of a second and in relation to behavior. Those modulations can happen without modulation of firing rates. When firing rates are modulated, the modulation of correlation is not related to it in a simple way. Moreover, the dynamic patterns of correlation depend on the distance between neurons. These findings support the notion that, in order to perform a computational task, neurons can associate rapidly into a functional group, while dissociating from concurrently activated competing groups., (Copyright (c) 1997 Wiley-Liss, Inc.)