Vagal nerve stimulation:A review of its applications and potential mechanisms that mediate its clinical effects

Vagal nerve stimulation (VNS) is an approved treatment for epilepsy and is currently under investigation as a therapy for other disorders, including depression, anxiety and Alzheimer's disease. This review examines the pre-clinical and clinical literature relating to VNS. A brief historical perspective is given, followed by consideration of the efficacy of the various clinical applications of VNS. Finally, what is known about the mechanism by which VNS exerts clinical benefit is considered. It is concluded that although the precise mechanism of action of VNS is still unknown, the search for the mechanism has the potential to lend new insight into the neuropathology of depression. It is important that prior assumptions about the influence of VNS on particular aspects of brain function do not constrain the investigations. (c) 2005 Elsevier Ltd. All rights reserved.</p

Deficits in response initiation, but not attention, following excitotoxic lesions of posterior parietal cortex in the rat

Damage to posterior parietal cortex in humans is known to cause hemineglect, and specifically difficulty in disengaging attention in tests of covert orienting. Aspirative lesions of a region of cortex in rats which is thought to be homologous to primate posterior parietal cortex has also been reported to cause what appears to be multimodal neglect. In order to make an assessment of the nature of this disorder, a variety of tests were employed: (1) a test of somatosensory neglect after Schallert et al. (Pharmacol. Biochem. Behav., 16 (1982) 455-462); (2) a skilled paw-reaching test after Whishaw et al. (Brain 109 (1986) 805-843); (3) a visual reaction time task with peripheral cues analogous to Posner's test of covert orienting (Q. J. Exp. Psychol., 32 (1980) 3-25). Following the posterior parietal lesion there was a global increase in reaction time of responses made contralateral to the lesion in the reaction time task, but there was no evidence of a deficit in covert orienting. There was also no evidence of somatosensory neglect. There was a decrease in the number of attempted reaches with the contralateral paw and a tendency to spend a smaller proportion of time in the contralateral half of the reaching cage. (C) 1997 Elsevier Science B.V.</p

Anticipatory errors after unilateral lesions of the subthalamic nucleus in the rat: Evidence for a failure of response inhibition

The nature of anticipatory responding in rats with unilateral subthalamic nucleus lesions was examined. Rats were trained to respond toward visual targets that were preceded by 1 of 4 different cues. For normal rats, a cue invokes an involuntary attentional orienting that enhances processing of the target at the location of attention. The cue is also a salient stimulus to which a response must be suppressed. Therefore, this task was used to investigate possible attentional impairments, as well as the ability of a lesioned rat to suppress competing motor programs. Responding under target control was not affected by the lesion. Then was an increase in anticipatory responses before target onset, which could be accounted for by a failure to inhibit contralateral responses.</p

Amphetamine and the adenosine A2A antagonist KW-6002 enhance the effects of conditional temporal probability of a stimulus in rats

As the length of foreperiod preceding an imperative signal increases, reaction time decreases and anticipatory (prior to the signal) responding increases. The authors designed a task to dissociate the effect of elapsing time in the foreperiod and conditional temporal probability of the imperative stimulus. The effects of 2 drugs--amphetamine and KW-6002--known to enhance the effect of foreperiod were compared. Three groups of rats were trained to respond to an auditory signal presented at 1 of 3 foreperiods, unpredictable from trial to trial. The length of preparation time was different for each group, but conditional temporal probability was the same. Reaction times were faster as a function of increased preparation time, whereas anticipatory responses were strongly modulated by conditional probability. Both amphetamine and KW-6002 speeded reaction times and increased anticipatory responding. The pattern of behavior was consistent with the suggestion that they enhanced the motor preparatory effects of conditional probability rather than speeded a timing process. The authors concluded that preparation time and expectancy (conditional temporal probability of an imperative signal) have differential effects on performance and that amphetamine and KW-6002 enhance the effect of expectancy. (APA PsycInfo Database Record (c) 2016 APA, all rights reserved

Covert orienting of attention in the rat and the role of striatal dopamine

Attention can be directed to a location in the absence of overt signs of orienting, a phenomenon termed ''covert orienting.'' The ability to orient attention covertly has been well documented in humans, but recent progress has been made with the operational definition of the processes involved in covert orienting. Reaction times to visual targets are quickened when attention is drawn to the location of the subsequent target, and processes such as disengagement, maintenance, and movement of attention can be dissociated by using this method. The possible involvement of striatal dopamine in covert orienting is disputed, with conflicting reports of deficits in covert orienting in patients with Parkinson's disease. To examine the significance of dopamine in the striatum in attentional processes, a test of covert orienting, analogous to that used in humans, was devised for the rat. Unilateral dopamine-depleting lesions of the striatum resulted in increases in mean reaction times contralateral to the side of the lesion, but reaction times did not change differentially as a function of the requirements to maintain, disengage, or shift attention. These findings add additional support to the hypothesis that the deficit that appears as hemineglect observed after striatal damage reflects a motor impairment rather than damage in neural systems underlying mechanisms for directing attention.</p

Attention to visual, but not tactile, properties of a stimulus results in activation of FOS protein in the visual thalamic reticular nucleus of rats

Previous reports have suggested that the modality-specific sectors of the thalamic reticular nucleus (TRN) may become selectively activated as a result of attention being drawn to their respective sensory modalities. Here we used a task that required the discrimination of digging bowls on the basis of their visual (the colour of the bowl) or tactile (the external texture of the bowl) characteristics. We trained rats to perform both modality discriminations, ensuring the equity of exposure to both visual and tactile aspects of the stimuli. On the test day, animals had to perform only one of the modality discriminations for a 1-h period prior to being transcardially perfused and their brains removed and processed for Fos immunocytochemistry. We found that animals that performed the visual discrimination prior to sacrifice demonstrated a selective activation of cells in the visual TRN. On the other hand, animals that had performed the tactile discrimination, despite encountering the same stimuli and having received equal visual stimulation as the animals performing the visual discrimination, did not have activation of the visual TRN. This evidence suggests that activation of visual TRN is a function of visual selective attention, and not merely visual stimulation. Surprisingly, the same was not true for somatic TRN, which was not labeled in any animals. It is possible that this lack of a double dissociation is the result of modality-specific differences in the attentional demands of the two discrimination tasks