The Affective and Neural Correlates of Heroin versus Cocaine Use in Addiction Are Influenced by Environmental Setting But in Opposite Directions.

Previous studies have shown that individuals with heroin and cocaine addiction prefer to use these drugs in distinct settings: mostly at home in the case of heroin and mostly outside the home in the case of cocaine. Here we investigated whether the context would modulate the affective and neural responses to these drugs in a similar way. First, we used a novel emotional task to assess the affective state produced by heroin or cocaine in different settings, based on the recollections of male and female drug users. Then we used fMRI to monitor neural activity during drug imagery (re-creating the setting of drug use) in male drug users. Consistent with our working hypothesis, the majority of participants reported a shift in the affective valence of heroin from mostly pleasant at home to mostly unpleasant outside the home (p < 0.0001). The opposite shift was observed for cocaine; that is, most participants who found cocaine pleasant outside the home found it unpleasant when taken at home (p < 0.0014). Furthermore, we found a double dissociation, as a function of drug and setting imagery, in BOLD signal changes in the left PFC and caudate, and bilaterally in the cerebellum (all p values <0.01), suggesting that the fronto-striatal-cerebellar network is implicated in the contextualization of drug-induced affect. In summary, we report that the same setting can influence in opposite directions the affective and neural response to psychostimulants versus opiates in humans, adding to growing evidence of distinct substrates for the rewarding effects of these two drug classes.SIGNIFICANCE STATEMENT The rewarding effects of addictive drugs are often thought to depend on shared substrates. Yet, environmental influences can unmask striking differences between psychostimulants and opiates. Here we used emotional tasks and fMRI to explore the influence of setting on the response to heroin versus cocaine in individuals with addiction. Simply moving from one setting to another significantly decreased heroin pleasure but increased cocaine pleasure, and vice versa. Similar double dissociation was observed in the activity of the fronto-striatal-cerebellar network. These findings suggest that the effects of opiates and psychostimulants depend on dissociable psychological and neural substrates and that therapeutic approaches to addiction should take into account the peculiarities of different drug classes and the settings of drug use.

Caloric Vestibular Stimulation Reduces Pain and Somatoparaphrenia in a Severe Chronic Central Post-Stroke Pain Patient: A Case Study.

Central post-stroke pain is a neuropathic syndrome characterized by intolerable contralesional pain and, in rare cases, somatic delusions. To date, there is limited evidence for the effective treatments of this disease. Here we used caloric vestibular stimulation to reduce pain and somatoparaphrenia in a 57-year-old woman suffering from central post-stroke pain. Resting-state functional magnetic resonance imaging was used to assess the neurological effects of this treatment. Following vestibular stimulation we observed impressive improvements in motor skills, pain, and somatic delusions. In the functional connectivity study before the vestibular stimulation, we observed differences in the patient's left thalamus functional connectivity, with respect to the thalamus connectivity of a control group (N = 20), in the bilateral cingulate cortex and left insula. After the caloric stimulation, the left thalamus functional connectivity with these regions, which are known to be involved in the cortical response to pain, disappeared as in the control group. The beneficial use of vestibular stimulation in the reduction of pain and somatic delusion in a CPSP patient is now documented by behavioral and imaging data. This evidence can be applied to theoretical models of pain and body delusions.

The sound of actions in apraxia.

Studies in nonhuman and human primates have demonstrated that sound-producing actions are mapped on the same mirror circuits that are activated during the visual recognition and execution of actions [1-12]. However, no causative link between the auditory recognition and execution of actions has been provided thus far. Here, we sought to determine whether patients with apraxia, who are by definition impaired in performing specific gestures, are also impaired in recognizing sounds specifically linked to human actions. Twenty-eight left-hemisphere-damaged patients with or without limb and/or buccofacial apraxia and seven right-hemisphere-damaged patients with no apraxia were asked to match sounds evoking human-related actions or nonhuman action sounds with specific visual pictures. Hand and mouth action-related sound recognition were specifically impaired in limb and buccofacial apraxia patients, respectively. Lesional mapping revealed that the left frontoparietal cortex is crucial for recognizing the sound of limb movements. By contrast, the left inferior frontal gyrus and adjacent insular cortex are causatively associated with recognition of buccofacial-related action sounds. These behavioral and neural double dissociations indicate that a left-lateralized multimodal mirror network is actively involved in the body-part-specific motor mapping of limb and mouth action-related sounds, as well as in the execution of the very same actions.

A selective representation of the meaning of actions in the auditory mirror system.

Mirror neurons in the monkey's premotor cortex respond during both execution and observation of actions and are thought to be critical for understanding others' actions. Human studies have shown premotor cortex activation while viewing actions, hearing their sounds, listening to or reading action-related sentences, and have compared execution and observation of similar actions. However, we still lack direct evidence in humans of the most striking and theoretically relevant feature of mirror neurons, i.e., that they map seen/heard actions onto motor representations of the same actions at an abstract level. Here we combine fast event-related functional magnetic resonance imaging with an unconscious semantic priming paradigm and show that the human auditory mirror system also holds an abstract representation of the meaning of heard actions. We analyzed the effect on brain activity of trial-by-trial semantic congruency between a target sound denoting a hand or mouth action (or an environmental event) and a briefly flashed written word acting as an unconscious cross-modal prime. Left inferior frontal and posterior temporal regions selectively responded to action sounds in a non-somatotopic fashion and were modulated by semantic congruency only in action sound trials. We also observed regions selective for either hand or mouth actions, which however did not show a corresponding effector-specific effect of semantic congruency. These results provide evidence that the human mirror system represents the meaning of actions (but not of other events) (a) at an abstract, semantic level, (b) independently of the effector, and (c) independently of conscious awareness.

Development of a rehabilitative program for unilateral neglect.

PURPOSE: The aim of the present paper is to review several studies which assessed the validity of a visuo-spatial training for the rehabilitation of neglect patients. In addition two peripheral stimulations (TENS and Optokinetic Stimulation) have been studied to assess the improvements of neglect disorders when used in combination with the visuo-spatial training. Also we analyzed the potential effect of training for attention on neglect and, viceversa, the effect of visuo-spatial training on attentional impairments. METHODS: the goals have been investigated by both group studies and descriptions of single cases. RESULTS: The visuo-spatial training produced significant improvements on the performance of neglect patients which generalized to every day living situations: the results showed to be stable over time and had positive effects on a variety of other neurological impairments. It was also shown that the improvements are confined to tasks involving spatial exploration of extrapersonal space, but did not extend to other neglect disorders, such as representational and personal neglect. The use of peripheral stimulations, at variance with other studies in the literature, did not add any advantage as compared to the improvements produced by the visuo-spatial training. No transfer between training for neglect and attention was observed. CONCLUSIONS: the present review pointed out that neglect disorders can be improved in a clinically meaningful way: the studies described also showed some limitations and proposed the need of further researches in order to extend the improvements to several other aspects of the neglect syndrome.

Between language and space: a cross-domain interaction.

We document for the first time the effect of a spatial deficit on an spoken language task. Right brain-damaged patients with and without neglect were administered a task of emphatic stress. Patients listened to 60 subject-verb-object sentence pairs. The emphatic stress could be placed on the subject, on the verb or on the object word. Patients had to judge whether the two sentences were same or different for the position of the emphatic stress. The judgements were more impaired in patients with neglect and when the stress was placed at the beginning of the sentence (on the subject word), that is to say, at the leftmost location of a hypothetical spatial representation of the heard sentence. We hypothesize that auditory language undergoes a spatial transcoding, and that this transcoding is affected by the presence of a spatial bias like that observed in patients with neglect.