Temporal Coding of Reward Value in Monkey Ventral Striatal Tonically Active Neurons.

The rostromedioventral striatum is critical for behavior dependent on evaluating rewards. We asked what contribution tonically active neurons (TANs), the putative striatal cholinergic interneurons, make in coding reward value in this part of the striatum. Two female monkeys were given the option to accept or reject an offered reward in each trial, the value of which was signaled by a visual cue. Forty-five percent of the TANs use temporally modulated activity to encode information about discounted value. These responses were significantly better represented using principal component analysis than by just counting spikes. The temporal coding is straightforward: the spikes are distributed according to a sinusoidal envelope of activity that changes gain, ranging from positive to negative according to discounted value. Our results show that the information about the relative value of an offered reward is temporally encoded in neural spike trains of TANs. This temporal coding may allow well tuned, coordinated behavior to emerge.SIGNIFICANCE STATEMENT Ever since the discovery that neurons use trains of pulses to transmit information, it seemed self-evident that information would be encoded into the pattern of the spikes. However, there is not much evidence that spike patterns encode cognitive information. We find that a set of interneurons, the tonically active neurons (TANs) in monkeys' striatum, use temporal patterns of response to encode information about the discounted value of offered rewards. The code seems straightforward: a sinusoidal envelope that changes gain according to the discounted value of the offer, describes the rate of spiking across time. This temporal modulation may provide a means to synchronize these interneurons and the activity of other neural elements including principal output neurons.

The role of the subthalamic nucleus in cognition.

Because the complex functions of the basal ganglia have been increasingly studied over the past several decades, the understanding of the role of the subthalamic nucleus (STN) in motor and cognitive functions has evolved. The traditional role in motor function ascribed to the STN, based on its involvement in the cortico-striato-thalamo-cortical motor loops, the pathologic STN activity seen in Parkinson's disease, and the benefits in motor symptoms following STN lesions and deep brain stimulation, has been revised to include wider cognitive functions. The increased attention focused on such nonmotor functions housed within the STN partially arose from the observed cognitive and affective side effects seen with STN deep brain stimulation. The multiple modalities of research have corroborated these findings and have provided converging evidence that the STN is critically involved in cognitive processes. In particular, numerous experiments have demonstrated the involvement of the STN in high-conflict decisions. The different STN functions appear to be related to activity in anatomically distinct subregions, with the ventral STN contributing to high-conflict decision-making through its role in the hyperdirect pathway involving the prefrontal cortex.

Predictors of Lamotrigine-associated rash.

PURPOSE: To determine the predictors of lamotrigine-associated rash (LTG-rash) and the incidence of serious and benign LTG-rash to individualize risk assessment in a given patient. METHODS: We reviewed the charts of all 988 outpatients seen at the Columbia Comprehensive Epilepsy Center between January 1, 2000, and December 31, 2003, who received LTG. Charts were reviewed for documentation of rash developing from any medication, including antiepileptic drugs (AEDs) and non-AEDs, and including remote histories of drug-related rashes. Demographics, medical history, and medication variables were tested as potential predictors of LTG-rash. RESULTS: Fifty-six (5.7%) of 988 patients experienced rash attributed to LTG, and 39 (3.9%) discontinued LTG because of rash. No patients experienced toxic epidermal necrolysis or required hospitalization because of LTG-rash. One case of mild probable Stevens-Johnson syndrome occurred. In multivariate analysis, a history of rash after another AED was the strongest predictor of LTG-rash (13.9% vs. 4.6%; OR = 3.62; p < 0.001), with children younger than 13 years also experiencing significantly more LTG-rash (10.7% vs. 4.3%; OR = 2.77; p < 0.001). In children with a rash attributed to another AED, 18.2% experienced LTG-rash, whereas in adults without a rash from another AED, 3% experienced LTG-rash. CONCLUSIONS: Based on this retrospective analysis, a history of another AED-related rash is the greatest risk factor for developing rash to LTG; age younger than 13 years is also a risk factor. Severe rash is rare when using the currently recommended titration rate.