Weak evidence for neural correlates of task-switching in macaque V1.

A central goal of systems neuroscience is to understand how populations of sensory neurons encode and relay information to the rest of the brain. Three key quantities of interest are 1) how mean neural activity depends on the stimulus (sensitivity), 2) how neural activity (co)varies around the mean (noise correlations), and 3) how predictive these variations are of the subject's behavior (choice probability). Previous empirical work suggests that both choice probability and noise correlations are affected by task training, with decision-related information fed back to sensory areas and aligned to neural sensitivity on a task-by-task basis. We used Utah arrays to record activity from populations of primary visual cortex (V1) neurons from two macaque monkeys that were trained to switch between two coarse orientation-discrimination tasks. Surprisingly, we find no evidence for significant trial-by-trial changes in noise covariance between tasks, nor do we find a consistent relationship between neural sensitivity and choice probability, despite recording from well-tuned task-sensitive neurons, many of which were histologically confirmed to be in supragranular V1, and despite behavioral evidence that the monkeys switched their strategy between tasks. Thus our data at best provide weak support for the hypothesis that trial-by-trial task-switching induces changes to noise correlations and choice probabilities in V1. However, our data agree with a recent finding of a single "choice axis" across tasks. They also raise the intriguing possibility that choice-related signals in early sensory areas are less indicative of task learning per se and instead reflect perceptual learning that occurs in highly overtrained subjects.NEW & NOTEWORTHY Converging evidence suggests that decision processes affect sensory neural activity, and this has informed numerous theories of neural processing. We set out to replicate and extend previous results on decision-related information and noise correlations in V1 of macaque monkeys. However, in our data, we find little evidence for a number of expected effects. Our null results therefore call attention to differences in task training, stimulus design, recording, and analysis techniques between our and prior studies.

Coherence between the hippocampus and anterior thalamic nucleus as a tool to improve the effect of neurostimulation in temporal lobe epilepsy: An experimental study.

BACKGROUND: Although the mechanisms by which deep brain stimulation (DBS) modifies the activity of the ictal network are mostly undefined, recent studies have suggested that DBS of the anterior nucleus of the thalamus (ANT) can be an effective treatment for mesial temporal lobe epilepsy (MTLE) when resective surgery cannot be performed. In a nonhuman primate (NHP) model of MTL seizures, we showed that the ANT was actively involved during interictal and ictal periods through different patterns and that the hippocampus (HPC) and ANT synchronously oscillate in the high beta-band during seizures. OBJECTIVE: Based on those findings, we evaluated whether the frequency of stimulation is an important parameter that interferes with seizures and how to adapt stimulation protocols to it. METHODS: We investigated the effects of low-frequency (40 Hz - determined as the ictal frequency of correlation between structures) and high-frequency (130 Hz - as commonly used in clinic) ANT stimulation in three monkeys in which MTLE seizures were initiated. RESULTS: Low-frequency stimulation had a strong effect on the number of seizures and the total time spent in seizure, whereas high-frequency stimulation had no effect. The coherence of oscillations between the HPC and the ANT was significantly correlated with the success of low-frequency stimulation: the greater the coherence was, the greater the antiepileptic effect of ANT-DBS. CONCLUSION: Our results suggest that low-frequency stimulation is efficient in treating seizures in a nonhuman primate model. More importantly, the study of the coherence between the ANT and HPC during seizures can help to predict the anti-epileptic effects of ANT stimulation. Furthermore, the DBS paradigm could be customized in frequency for each patient on the basis of the coherence spectral pattern.

Implication of Anterior Nucleus of the Thalamus in Mesial Temporal Lobe Seizures.

Deep brain stimulation of the anterior nucleus of the thalamus has been proposed as novel therapy to treat intractable epilepsy. To optimize this approach, we proposed to study the involvement of this nucleus in a non-human primate model of mesial temporal lobe seizure. Two macaques were implanted with one chronic electrode into the hippocampus allowing to monitor the ictal activity. Neurons of the anterior nucleus of the thalamus were recorded with a microelectrode inserted acutely. To induce seizures, penicillin was injected into the hippocampus and neuronal activities of the anterior nucleus were analyzed during ictal and interictal periods. The effects of the chemical neuromodulation of the anterior nucleus on the ictal hippocampal activities were studied and electron microscopy analysis was carried out to study morphological modifications induced in the anterior nucleus of the thalamus. Our results demonstrate that the anterior nucleus of the thalamus is directly involved in the pathophysiology of induced seizures since: (1) Electrophysiological study showed an heterogenous excitation during seizure characterized by the appearance of 2 types of neuronal firing response; (2) chemical neuromodulation of the anterior nucleus of the thalamus changed the severity of seizures; (3) morphological modification of the ultrastructure as well as a reduction of synapse density were observed within the ipsilateral anterior nucleus of the thalamus. This study demonstrates that the anterior nucleus of the thalamus is part of the epileptic network activated during temporal lobe seizures and suggests that this nucleus would be valid target for seizure control using deep brain stimulation.

An on demand macaque model of mesial temporal lobe seizures induced by unilateral intra hippocampal injection of penicillin.

PURPOSE: Our objective was to propose a new on demand non-human primate model of mesial temporal lobe seizures suitable for pre-clinical innovative therapeutic research. METHODS: Five macaques were stereotaxically implanted unilaterally with a deep recording electrode in the hippocampus. For each experiment, penicillin was injected into the hippocampus and animals were monitored during five consecutive hours. A total of 12-27 experiments with a mean cumulative dose of 162644 ±â€¯70190 UI of penicillin have been performed per animal Injections were repeated at least once a week over a period of 98-276 days. The time-course of electro-clinical seizures and the response to diazepam have been quantified from, respectively, 84 and 11 experiments randomly selected. To evaluate brain injury produced by several penicillin injections and to characterize the changes occurring into the hippocampus, we performed an histological analysis, including neuronal nuclei and glial fibrillary acid protein immunostaining and electron microscopy. RESULTS: After each penicillin injection, we observed that the electro-clinical characteristics were reproducible among non-human primates and experiments. Seizures duration was stable (29.60 ±â€¯6.62 s) and the frequency of seizures reached a plateau with about 3 seizures/20 min during 180 min and that could be useful to test new treatments. Diazepam did not modify the course of the seizures. Hippocampal sclerosis was found similar to that encountered in epileptic patients with a neuronal loss and a glial cells proliferation. Electron microscopy analysis of CA1 revealed a decreased number of synapses and a large amount of glial fibrillary filaments in the injected hippocampus. Interestingly, this on-demand model of seizure, turned into a chronic model with spontaneous occurrence of seizures after a cumulative amount ranging from 119 to 145 KIU of penicillin injected. CONCLUSION: The present study shows that an on-demand model of mesial temporal lobe seizure can be developed by intra-hippocampal injection of penicillin. The seizures are reproducible, stable and resistant to diazepam. Brain damages are confined to the hippocampus with similar features to that found in human mesial temporal lobe epilepsy. This model reproduces the symptomatogenic and the irritative zone usually seen in human MTLE, with the additional advantage of having a clear delineation of the epileptogenic zone. However, the mechanism of actions of the penicillin as a proconvulsant agent does not replicate all of the much more complex physiological and cellular mechanisms that are involved in human epilepsy and represent a limitation of our study that one must be aware of.