Shared Neural Mechanisms for the Evaluation of Intense Sensory Stimulation and Economic Reward, Dependent on Stimulation-Seeking Behavior.

UNLABELLED: Why are some people strongly motivated by intense sensory experiences? Here we investigated how people encode the value of an intense sensory experience compared with economic reward, and how this varies according to stimulation-seeking preference. Specifically, we used a novel behavioral task in combination with computational modeling to derive the value individuals assigned to the opportunity to experience an intense tactile stimulus (mild electric shock). We then examined functional imaging data recorded during task performance to see how the opportunity to experience the sensory stimulus was encoded in stimulation-seekers versus stimulation-avoiders. We found that for individuals who positively sought out this kind of sensory stimulation, there was common encoding of anticipated economic and sensory rewards in the ventromedial prefrontal cortex. Conversely, there was robust encoding of the modeled probability of receiving such stimulation in the insula only in stimulation-avoidant individuals. Finally, we found preliminary evidence that sensory prediction error signals may be positively signed for stimulation-seekers, but negatively signed for stimulation-avoiders, in the posterior cingulate cortex. These findings may help explain why high intensity sensory experiences are appetitive for some individuals, but not for others, and may have relevance for the increased vulnerability for some psychopathologies, but perhaps increased resilience for others, in high sensation-seeking individuals. SIGNIFICANCE STATEMENT: People vary in their preference for intense sensory experiences. Here, we investigated how different individuals evaluate the prospect of an unusual sensory experience (electric shock), compared with the opportunity to gain a more traditional reward (money). We found that in a subset of individuals who sought out such unusual sensory stimulation, anticipation of the sensory outcome was encoded in the same way as that of monetary gain, in the ventromedial prefrontal cortex. Further understanding of stimulation-seeking behavior may shed light on the etiology of psychopathologies such as addiction, for which high or low sensation-seeking personality has been identified as a risk factor.

Rate-dependent effects of monoamine releasers on intracranial self-stimulation in rats: implications for abuse liability assessment.

'Rate dependency' in the discipline of behavioral pharmacology describes a phenomenon wherein the effect of a drug on the rate of a behavior varies systematically as a function of the baseline, predrug rate of that behavior. Historically, rate-dependency studies have compared drug effects on different baseline rates of behavior maintained either by different schedules of reinforcement or during sequential segments of a fixed-interval schedule. The current experiment generated different baseline rates of behavior by altering frequency of electrical stimulation in an intracranial self-stimulation assay. Amphetamine and 10 other monoamine releasers were analyzed for their ability to produce rate-dependent effects in this assay. There were three main findings. First, all compounds produced rate-dependent effects at some dose. Second, one parameter of rate-dependency plots (peak Y-intercept of the regression line) correlated with in-vitro neurochemical data on selectivity of these compounds to release dopamine versus serotonin (P<0.025, R=0.50). Lastly, a correlation between peak Y-intercept and breakpoints under a progressive-ratio procedure in nonhuman primates was also significant (P<0.05, R=0.64). Overall, these results extend the rate-dependent effects of monoamine releasers to behavior maintained under intracranial self-stimulation and suggest that, at least for monoamine releasers, the Y-intercept parameter of rate-dependency plots might be a useful metric of drug reward and predictor of drug self-administration measures of drug reinforcement.

Increase in accumbal dopaminergic transmission correlates with response cost not reward of hypothalamic stimulation.

Rats were trained to lever-press for intracranial self-stimulation (ICSS) of the lateral hypothalamus on either a fixed ratio (FR) 1 or 10 schedule. Their brains were removed after a 20 min session and tissue punches taken from the nucleus accumbens, olfactory tubercle, anterior striatum, or central striatum. These punches were assayed for content of dopamine (DA) and the major DA metabolite DOPAC. Compared with implanted controls, only the FR10 group showed significantly elevated DOPAC/DA ratios. These elevations were statistically significant in nucleus accumbens and central striatum and near significance in anterior striatum. They occurred to similar degrees in each hemisphere. In contrast, we found that stimulation of the ventral tegmental area of anesthetized rats asymmetrically increased the DOPAC/DA ratio, being most prominent in the ipsilateral accumbens. Because the FR10 group made only 58% of the responses of the FR1 group and received only 6% of the stimulations of the FR1 group, yet unlike the FR1 group showed a significant increase in the DOPAC/DA ratio, we suggest that the DA release was primarily influenced by the schedule, not the stimulation or the reward of the stimulation. These results were interpreted in terms of a model in which hypothalamic ICSS reward is largely dependent on non-dopaminergic mechanisms, with accumbal DA transmission being strongly dependent on the costs versus benefits of ongoing behavior.

Economic substitutability of electrical brain stimulation, food, and water.

Concurrent variable-ratio schedules of electrical brain stimulation, food, and water were paired in various combinations as reinforcement of rats' lever presses. Relative prices of the concurrent reinforcers were varied by changing the ratio of the response requirements on the two levers. Economic substitutability, measured by the sensitivity of response ratio to changes in relative price, was highest with brain stimulation reinforcement of presses on both levers and lowest with food reinforcement of presses on one lever and water reinforcement of presses on the other. Substitutability with brain stimulation reinforcement of presses on one lever and either food or water reinforcement for presses on the other was about as high as with brain stimulation for presses on both levers. Electrical brain stimulation for rats may thus serve as an economic substitute for two reinforcers, neither of which is substitutable for the other.

Assessment of the neural substrate for intracranial self-stimulation by the postreinforcement pause technique.

The poststimulation excitability of neurons mediating intracranial self-stimulation (ICSS) was evaluated by the paired-pulse method. Stimulus effectiveness was assessed by the postreinforcement pause (PRP) and by frequency threshold (FT) determinations in 7 rats performing ICSS in the medial forebrain bundle (MFB) and in the ventral tegmental area (VTA). Stimulus effectiveness values were minimal at conditioning-test (C-T) pulse intervals of 0.6 and 0.8 ms for MFB and VTA animals, respectively, because of neuronal refractoriness. Local potential summation could account for the increase in effectiveness at very short C-T intervals, and an additional peak of enhanced effectiveness at a C-T interval of 2.0 ms, perhaps reflecting synaptic events, was observed only in VTA animals with the PRP method. Important advantages of the PRP method were that the C-T interval was the only stimulus parameter that was varied, and the behavioral output of the animal remained relatively constant.

A low-cost, 3 channel neural stimulator.

An inexpensive design using minimal components is generally described. A choice is provided for the behaving animal between 2 primary channels that are disabled once the choice is made. A third channel acts as the reset and must be activated after each choice is made of the primary channels. Each channel is capable of providing independent control over pulse train duration, frequency and voltage. The reset channel may be electrically silent if desired. An innovative use is made of high output impedance solid state analog switches to isolate the outputs of the 3 channels as they are connected together to the single ICS electrode.

Simultaneous rate-independent and rate-dependent assessment of intracranial self-stimulation: evidence for the direct involvement of dopamine in brain reinforcement mechanisms.

A two-level intracranial self-stimulation (ICSS) paradigm was developed in which both rate-independent and dependent measures of ICSS could be obtained simultaneously. Responses at the first lever resulted in stimulation which decreased in magnitude after every fifth response, while responses at the second lever reset the current available. The current at which the reset responses occurred was defined as the 'reward threshold'. In addition, the rate of responding was determined at each current for which the animals responded during this stimulate-reset sequence. Decreased reward following treatment with the neuroleptic pimozide, a specific blocker of dopamine receptors, was demonstrated by an elevated 'reward threshold'. The same effect could be obtained in control animals by making each stimulation less rewarding, i.e., by decreasing the amount of charge per stimulation. Pimozide increased 'reward threshold' without a generalized disruption of response rates. While rates were decreased at low currents they were unchanged at high currents. 'Reward threshold' was decreased following D-amphetamine treatment, and was accompanied by a dose-related decrease in response rates at high to medium current intensities. These data suggest that neuroleptic attenuation of ICSS is due to diminished reward and not to motor deficits. Further, due to the specificity of pimozide, they suggest a direct role for dopamine in the mediation of reward.

[Assessment of the reinforcing properties of self stimulation in rats using the "discordance" index]. / Otsenka podkrepliaiushchikh svoistv samostimuliatsii u krys s pomoshch'iu pokazatelia "rassoglasovaniia"

Histogramms of the duration of pedal pressing (PDH) as a function of stimulation parameters, were studied in fifteen rats with electrodes inserted in the lateral hypothalamus and with fixed series of brain stimulation. The "discordance" parameter was used to estimate the changes in PDH modes relative to the moment of the end of brain stimulation. It was found that an increase in the stimulation charge brought about a gradual replacement of positive discordance (the duration of pressing exceeds that of stimulation) by a negative one (duration of pressing is shorter than that of stimulation) and a rise of negative discordance. It is assumed that in the case of positive discordance the duration of the total brain stimulation possesses reinforcing properties, while in the case of negative discordance the beginning of the stimulation possesses reinforcing properties, and its continuation becomes negative.