Background: Recently, anterior limb of the internal capsule and nucleus accumbens deep brain stimulation (DBS) has been used in the treatment of medication-refractory obsessive-compulsive disorder (OCD). This region has been previously explored with lesion therapy, but with the advent of DBS there exists the possibility of monitoring the acute and chronic effects of electrical stimulation. The stimulation-induced benefits and side effects can be reversibly and blindly applied to a variety of locations in this region. Objective: To explore the acute effects of DBS in the anterior limb of the internal capsule and nucleus accumbens region. Methods: Ten total DBS leads in five patients with chronic and severe treatment-refractory OCD were tested. Patients were examined 30 days after DBS placement and received either ''sham'' testing or actual testing of the acute effects of DBS (the alternative condition tested 30 days later). Results: Pooled responses were reviewed for comparability of distribution using standard descriptive methods, and relationships between the variables of interest were sought using x 2 analysis. A total of 845 stimulation trials across the five patients were recorded and pooled. Of these 16% were elicited from sham stimulation and 17% from placebo (0 V stimulation). A comparison of active to sham trials showed that sham stimulation was not associated with significant side effects or responses from patients. Non-mood-related responses were found to be significantly associated with the ventral lead contacts (0 and 1) (p = 0.001). Responses such as taste, smell and smile were strongly associated with the most ventral lead positions. Similarly, physiological responses-for example, autonomic changes, increased breathing rate, sweating, nausea, cold sensation, heat sensation, fear, panic and panic episodes-were significantly associated with ventral stimulation (p = 0.001). Fear and panic responses appeared clustered around the most ventral electrode (0). Acute stimulation resulted in either improved or worsened mood responses in both the dorsal and ventral regions of the anterior limb of the internal capsule. Conclusion: The acute effects of DBS in the region of the anterior limb of the internal capsule and nucleus accumbens, particularly when obtained in a blinded fashion, provide a unique opportunity to localise brain regions and explore circuitry.

The amygdala is closely linked to basal ganglia circuitry and plays a key role in danger detection and fear-potentiated startle. Based on recent findings of amygdalar abnormalities in Parkinson's disease, we hypothesized that non-demented patients with this illness would show blunted reactivity during aversive/unpleasant events, as indexed by diminished emotional modulation of the startle eyeblink response. To test this hypothesis, 23 idiopathic patients with Parkinson's disease and 17 controls viewed standardized sets of aversive, pleasant and neutral pictures for 6 s each. During this time, white noise bursts (50 ms, 95 db) were binaurally presented to elicit startle eyeblink responses, measured from electrodes over the orbicularis oculi. After viewing each picture, subjects provided ratings of valence and arousal. The Parkinson's disease patients were in the early to middle stages of their disease, not demented or depressed, and were tested 'on' dopaminergic medication. The two groups were similar in age, education, gender and cognitive screening status. The control group had larger startle responses when viewing negative, aversive pictures than neutral or pleasant pictures. As predicted, startle enhancement during aversive pictures was significantly muted in the Parkinson's disease patients. This blunting was not due to abnormalities in the mechanics of the startle eyeblink per se. Nor was it related to depression symptoms, medications (psychotropics), or failure to perceive/appreciate the negative meaning of aversive pictures (i.e. normal valence ratings). Reduced startle reactivity in the disease group was related to disease severity (Hoehn-Yahr) and occurred in the context of reduced arousal ratings of aversive pictures. These findings of blunted startle reactivity add to the literature on emotional changes associated with Parkinson's disease. The basis for this muted reactivity is unknown but may involve an amygdala-based translational defect whereby the results of cognitive appraisal are not appropriately transcoded into somato-motor-arousal responses normally associated with an aversive motivational state. This may arise from faulty dopaminergic gating of the amygdala, resulting in 'inhibition' of the amygdala in the manner described by Marowsky et al. (Marowsky A, Yanagawa Y, Obata K, Vogt E. Neuron 2005; 48: 1025-37). More broadly, the findings of muted reactivity to aversive stimuli may reflect a 'bradylimbic' affective disturbance in patients with Parkinson's disease. Future studies are needed to address whether the physiologic blunting observed here might be a useful correlate of apathy.

Emotion researchers often categorize angry and fearful face stimuli as "negative" or "threatening". Perception of fear and anger, however, appears to be mediated by dissociable neural circuitries and often elicit distinguishable behavioral responses. The authors sought to elucidate whether viewing anger and fear expressions produce dissociable psychophysiological responses (i.e., the startle reflex). The results of two experiments using different facial stimulus sets (representing anger, fear, neutral, and happy) indicated that viewing anger was associated with a significantly heightened startle response (p < .05) relative to viewing fear, happy, and neutral. This finding suggests that while anger and fear faces convey messages of "threat", their priming effect on startle circuitry differs. Thus, angry expressions, representing viewer-directed threat with an unambiguous source (i.e., the expresser), may more effectively induce a motivational propensity to withdraw or escape. The source of threat is comparatively less clear for fearful faces. The differential effects of these two facial threat signals on the defensive motivational system adds to growing literature highlighting the importance of distinguishing between emotional stimuli of similar valence, along lines of meaning and functional impact.

DBS in the region of the nucleus accumbens produced smile and euphoria suggesting that alterations in the ventral striatum may result in emotional experience and displays. We hypothesize the existence of a limbic-motor network responsible for such changes. This observation suggests that DBS may be useful as a therapy for mood disorders.