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.

Does field independence predict visuo-spatial abilities underpinning human navigation? Behavioural evidence.

Field independence (FI) has been defined as the extent to which the individual perceives part of a field as discrete from the surrounding field, rather than embedded in the field. It has been proposed to represent a relatively stable pattern in individuals' predisposition towards information processing. In the present study, we assessed the effect of FI on skills underpinning human navigation. Fifty Healthy individuals took part in this study. FI has been assessed by using the group embedded figures test (GEFT). Participants were also asked to perform several visuo-spatial orientation tasks, including the perspective taking/spatial orientation test (PTSOT), the mental rotation task (MRT) and the vividness task, as well as the Santa Barbara Sense of Direction Scale, a self-reported questionnaire, which has been found to predict environmental spatial orientation ability. We found that performances on the GEFT significantly predicted performances on the PTSOT and the MRT. This result supports the idea that FI predicts human navigation.

Right but not left angular gyrus modulates the metric component of the mental body representation: a tDCS study.

The parietal lobes contribute to body-space representation. The present work aims at characterizing the functional role of the inferior parietal lobe in body-space representation and at studying the different roles of the angular gyrus in the right and left hemisphere. We conducted three separate transcranial direct current stimulation (tDCS) experiments using "tactile distance task" as an implicit measure of body representation. Whereas anodal tDCS on the right angular gyrus influences vocal reaction times (vRT) for stimuli delivered on the ipsilateral body parts without changes of accuracy, right tDCS improved both vRT and accuracy for tactile stimuli on the contralateral limbs. Sham or left parietal anodal tDCS had no effect. These evidences support the view that right parietal areas have a crucial role in the metric component of the body representation.

The unexplored link between aesthetic perception and creativity: A theory-driven meta-analysis of fMRI studies in the visual domain.

Creative production (related to art-making) and aesthetic appreciation (related to art-viewing) are inherently linked in visual arts, but their relationship has never been explored explicitly in cognitive neuroscience, nor the nature of such connection. The available literature suggests two cognitive processes as possible foundations of these two experiences: motor simulation or inhibitory control. In a meta-analysis of fMRI studies, we addressed this issue: we investigated whether there are shared neurofunctional underpinnings behind aesthetic and creative experiences in the visual domain; further, we examined whether any shared brain activation may reflect either motor simulation or inhibitory processes. A conjunction analysis revealed a common involvement of the pre-SMA in both classes of studies, a brain region, if anything, more concerned with top-down inhibitory motor and volitional cognitive control rather than bottom-up motor simulation. In the art-viewing domain, this finding was primarily driven by figurative rather than abstract art. The methodological limitations in the available literature are discussed together with possible new ways to expand the existing findings.

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.

Is Right Angular Gyrus Involved in the Metric Component of the Mental Body Representation in Touch and Vision? A tDCS Study.

Several studies have found in the sense of touch a good sensory modality by which to study body representation. Here, we address the "metric component of body representation", a specific function developed to process the discrimination of tactile distances on the body. The literature suggests the involvement of the right angular gyrus (rAG) in processing the tactile metricity on the body. The question of this study is the following: is the rAG also responsible for the visual metric component of body representation? We used tDCS (anodal and sham) in 20 subjects who were administered an on-body distance discrimination task with both tactile and visual stimuli. They were also asked to perform the same task in a near-body condition. The results allow us to confirm the role of rAG in the estimation of tactile distances. Further, we also showed that rAG might be involved in the discrimination of distances on the body not only in tactile but also in visual modality. Finally, based on the significant effects of anodal stimulation even in a near-body visual discrimination task, we proposed a higher-order function of the AG in terms of a supramodal comparator of quantities.

Two forms of touch perception in the human brain.

We compared the judgment of distance between two simultaneous tactile stimuli applied to different body parts, with judgment of intensity of skin contact of the very same stimulation. Results on normal subjects showed that both tasks bilaterally activate parietal and frontal areas. However, the evaluation of distances on the body surface selectively activated the angular gyrus and the temporo-parieto-occipital junction in the right hemisphere. The different involvement of the brain areas in the two tactile tasks is interpreted as the need for using a Mental Body Representation (MBR) in the distance task, while the judgment of the intensity of skin deflection can be performed without the mediation of the MBR. The present study suggests that the cognitive processes underlying the two tasks are supported by partially different brain networks. In particular, our results show that metric spatial evaluation is lateralized to the right hemisphere.

Depression disorder in patients with cerebellar damage: Awareness of the mood state.

BACKGROUND: Although depressive symptoms are often reported to be comorbid with degenerative cerebellar diseases, the role of the cerebellum in depressive disorder needs to be elucidated. To address this aim, we investigated self-perception of the negative mood state in patients with cerebellar pathology and depressive symptoms. METHODS: Thirty-eight patients with cerebellar damage (10 with depressive symptoms - CB-DP and 28 with no depressive symptoms - CB-nDP), 11 subjects with depressive disorders without cerebellar damage (DP) and 29 healthy controls (CTs) were enrolled. A device for self-monitoring of the mood state (MoMo) and validated scales such as the Profile of Mood States questionnaire (POMS), the Self-Report Symptom Inventory-Revised (SCL-90-R) and the Hamilton Depression Rating Scale (HDRS) were used to evaluate depressive symptoms. RESULTS: Both CB-DP and DP patients showed higher scores than CTs on the POMS and SCL-90-R for depressive factors and on the HDRS. DP patients showed a lower frequency of 'good' mood and a higher frequency of 'bad' mood than CTs when using the MoMo device. However, although the two depressed populations showed comparable scores on these validated scales, CB-DP patients showed impaired self-awareness of the mood experience in 'the here and now', as evidenced by the absence of significant differences, compared with CTs, in the subjective mood evaluation performed with the MoMo device. LIMITATIONS: The number of CB patients and inhomogeneity across MRI scans were study limitations. CONCLUSION: Cerebellar dysfunction might slow the data integration necessary for mood state awareness, resulting in difficulty of depressed CB patients in explicitly recognizing their mood "in the here and now".

Neural bases of personal and extrapersonal neglect in humans.

Human awareness of left space may be disrupted by cerebral lesions to the right hemisphere (hemispatial neglect). Current knowledge on the anatomical bases of this complex syndrome is based on the results of group studies that investigated primarily the best known aspect of the syndrome, which is visual neglect for near extrapersonal (or peripersonal) space. However, another component-neglect for personal space-is more often associated with, than double-dissociated from, extrapersonal neglect, especially, in chronic patients. The present investigation aimed at exploring the anatomical substrate of both extrapersonal and personal neglect by using different advanced methodological approaches to lesion-function correlation. Fifty-two right ischaemic patients were submitted to neuropsychological assessment and in-depth MRI evaluation. The borders of each patient's lesion were delimited onto its own high-resolution anatomical image and then submitted to an automated spatial normalization algorithm. Besides conventional lesion density plots and subtraction analysis, region-based statistical analyses were performed on percentage values of the lesioned tissue also using a new parcellation of the white matter (WM). Data were finally submitted to voxelwise statistical analysis using a recently proposed method (voxel-based lesion-symptom mapping). Results converged in showing that awareness of extrapersonal space is based on the integrity of a circuit of right frontal (ventral premotor cortex and middle frontal gyrus) and superior temporal regions, whereas awareness of personal space is rooted in right inferior parietal regions (supramarginal gyrus, post-central gyrus and especially the WM medial to them). Common but less crucial regions for both neglect sub-types were located in the temporo-peri-Sylvian cortex. We suggest that extrapersonal space awareness critically involves a ventral circuit recently described for the exogenous allocation and reorienting of attention in space. Disruption of personal space awareness, instead, seems to be due to a functional disconnection between regions important for coding proprioceptive and somatosensory inputs, and regions coding more abstract egocentric representations of the body in space. In conclusion, present data strongly support a segregation of personal and extrapersonal spatial awareness in humans, both from a functional and an anatomical point of view.

Personal neglect: A comprehensive theoretical and anatomo-clinical review.

Personal neglect (PN) is the hemi-inattention toward the contralesional bodily space that follows a cerebral lesion, usually to the right hemisphere. OBJECTIVE: To provide a historical, comprehensive review of the different theoretical accounts, of the available diagnostic measures, of the relationship with different body representation disorders, and of recovery-related issues. Moreover, to review the anatomo-functional correlates of PN, focusing on group studies that used modern voxel-based lesion-symptoms mapping. METHOD: PubMed database was searched for all the available studies on PN conducted in the last 30 years. Relevant clinical data for each study were reported in a table, which was used as a reference for developing the discussion on the points of interest. RESULTS: Evaluation tools for PN suffer from limitations and should include both face- and body-related testing as well as require both basic exploration and object use in the same personal space. Dedicated rehabilitative procedures are lacking and advocated, given that recovery of PN and extrapersonal neglect can be dissociated and their degree is not correlated. PN is almost constantly associated with a cohort of body representation disorders that do not reveal themselves unless specifically investigated. PN is significantly correlated to alterations at the level of both the anterior parietal cortex and the underlying fronto-parietal fiber bundles. CONCLUSIONS: The discussed data point to the need for a diagnostic and rehabilitative update. Following the topological and hodological lesional pattern, PN might emerge from the combination of a body representation disorder and a spatial inattention for half of the space. (PsycINFO Database Record

When space merges into language.

We present data from right brain-damaged patients, with and without spatial heminattention, which show the influence of hemispatial deficits on spoken language processing. We explored the findings of a previous study, which used an emphatic stress detection task and suggested spatial transcoding of a spoken active sentence in a 'language line'. This transcoding was impaired in its initial portion (the subject-word) when the neglect syndrome was present. By expanding the original methodology, the present study provides a deeper understanding of the level of spoken language processing involved in the heminattentional bias. To ascertain the role played by syntactic structure, active and passive sentences were compared. Sentences comprised of musical notes and of a sequence of unrelated nouns were also compared to determine whether the bias was manifest with any sequence of events (not only linguistic ones) deployed over time, and with a sequence of linguistic events not embedded in a structured syntactic frame. Results showed that heminattention exerted an influence only when a syntactically structured linguistic input (=sentence with agent of action, action and recipient of action) was processed, and that it did not interfere when a sequence of non-linguistic sounds or unrelated words was presented. Furthermore, when passing from active to passive sentences, the heminattentional bias was inverted, suggesting that heminattention primarily involves the logical subject of the sentence, which has an inverted position in passive sentences. These results strongly suggest that heminattention acts on the spatial transcoding of the deep structure of spoken language.

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.

Recovery of personal neglect.

BACKGROUND: Extrapersonal unilateral spatial neglect after stroke is associated to a poor rehabilitation outcome. Minor attention has been paid to the recovery of personal neglect, to its relationship with the recovery of extrapersonal neglect and of independency in activities of daily living. AIM: The present study aims at evaluating whether there is an association between recovery of extrapersonal and personal neglect. The secondary aim was to investigate if personal neglect may affect the effectiveness of neurorehabilitation in patients with subacute stroke. DESIGN: Observational study. SETTING: Neurorehabilitation Hospital in Rome, Italy, inpatients. POPULATION: A sample of 49 patients with unilateral spatial neglect resulting from right ischemic cerebral infarction was enrolled in this study, divided into three subgroups according to the presence and the degree of personal neglect, and evaluated pre and postneurorehabilitation. METHODS: Personal neglect was evaluated using Zoccolotti and Judica's Scale, extrapersonal neglect using Letter Cancellation Test, Barrage Test, Sentence Reading Test and Wundt-Jastrow Area Illusion Test. Barthel Index (BI), Rivermead Mobility Index, and Canadian Neurological Scale were also administered. RESULTS: Results showed the following: 1) recovery of personal neglect was not significantly correlated with that of extrapersonal neglect, despite both the disorders were ameliorated after a "non-specific" rehabilitation treatment; 2) personal neglect per se was not an additional negative prognostic factor in the rehabilitation findings. CONCLUSIONS: Our results suggested that the recoveries of the two types of neglect are independent from each other, and that the presence of personal neglect does not imply significant additional problems to the functional outcomes. CLINICAL REHABILITATION IMPACT: Our study highlighted the need of novel tools to assess the presence and to improve the recovery of personal neglect.

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.

Representational neglect and navigation in real space.

Topographical orientation relies on several cognitive strategies adopted by humans to move within the environment. In the present study, we investigate whether mental representation disorders affect specific cognitive mechanisms subserving human orientation. In order to differentiate distinct cognitive mechanisms involved in topographical orientation, we created a human version of the well-known "Morris Water Maze" and tested left and right brain damaged patients in a place-learning task. The test required the subjects to explore an experimental room in which no visual cues were present, find a target location, and then reach it in different conditions. The ability to memorize target locations in short- and long-term memory was also assessed. We found that all participants were able to reach the target location by using idiothetic cues (vestibular inputs, motor efferent copy, etc.). On the other hand, when starting position changed and re-orientation was necessary to reach the target location, in order to compute a new trajectory, only patients affected by representational neglect got lost. These results provide the first neuropsychological evidence of involvement of mental representation in a specific cognitive process allowing humans to reach a target place from any location in the environment.

Analyzing aphasia data in a multidimensional symptom space.

The utility of single-case vs. group studies has been debated in neuropsychology for many years. The purpose of the present study is to illustrate an alternative approach to group studies of aphasia, in which the same symptom dimensions that are commonly used to assign patients to classical taxonomies (fluency, naming, repetition, and comprehension) are used as independent and continuous predictors in a multivariate design, without assigning patients to syndromes. One hundred twenty-six Italian-speaking patients with aphasia were first classified into seven classic aphasia categories, based on fluency, naming, auditory comprehension, and repetition scales. There were two goals: (1) compare group analyses based on aphasia types with multivariate analyses that sidestep classification and treat aphasic symptoms as continuous variables; (2) present correlation-based outlier analyses that can be used to identify individuals who occupy unusual positions in the multivariate "symptom space." In the service of the first goal, group performance on an external validation measure (the Token Test) was assessed in three steps: analyses of variance based on aphasia type, regressions using the same cut-offs for fluency, naming, comprehension and repetition as independent but dichotomous predictors, and regressions using the same subscales as continuous predictors (with no cut-offs). More variance in Token Test performance was accounted for when symptoms were treated as continuous predictors than with the other two methods, though use of independent but dichotomous predictors accounted for more variance than aphasia taxonomies. Thus, if we by-pass classical taxonomies and treat patients as points in a multidimensional symptom space, better predictions are obtained. Outlier analyses show that group results depend on heterogeneity among patients, which can be used as a search tool to identify potentially interesting dissociations. Hence this multivariate group approach is complementary to and compatible with single-case methods.

The two dimensions of the body representation in women suffering from Anorexia Nervosa.

A core symptom of Anorexia Nervosa (AN) is a severe alteration of body representations. Evidence from somatoperception studies point to a generic disturbances of somatosensory components of body representations. Here we have investigated whether AN patients (N=18) and controls differed in the perception of tactile stimuli differently oriented along the body axes. We tested the hypothesis that patients perceive and represent their body selectively larger in only one dimension. To this aim we used elementary tactile measures for tactile acuity (Von Frey's test and two-point discrimination thresholds - 2PD) and tactile discrimination measures. The rationale is based on the assumption that AN patients have a wider body representation, and that tactile body representation tasks (Tactile Distance task) oriented across the bodies (horizontally) are influenced by distorted body representations compared with tactile stimuli oriented along the bodies (vertically) which should not be influenced by body representations. Results showed that patients judged horizontal tactile stimuli significantly wider than the same stimuli oriented vertically.These results suggest that human brain perceives things differently based on body representations and that the beliefs concerning body size influence the specific somatosensory process of tactile experience.

Emotional susceptibility trait modulates insula responses and functional connectivity in flavor processing.

The present study aimed at investigating the relationship between Emotional Susceptibility (ES), an aspect of the personality trait Neuroticism, and individual differences in the neural responses in anterior insula to primary sensory stimuli colored by affective valence, i.e., distasting or pleasantly tasting oral stimuli. In addition, it was studied whether intrinsic functional connectivity patterns of brain regions characterized by such differential responses could be related to ES. To this purpose 25 female participants underwent functional magnetic resonance imaging scanning, while being involved in a flavor experiment. During the experiment, flavor stimuli were administered consisting of small amounts of liquid with a different affective valence: neutral, pleasant, unpleasant. The results showed that individual differences in ES trait predicted distinct neural activity patterns to the different stimulus conditions in a region of left anterior insula that a previous meta-analysis revealed to be linked with olfacto-gustatory processing. Specifically, low ES was associated with enhanced neural responses to both pleasant and unpleasant stimuli, compared to neutral stimuli. By contrast, high ES participants showed equally strong neural responses to all types of stimuli without differentiating between the neutral and affective stimuli. Finally, during a task-free state, high ES trait appeared also to be related to decreased intrinsic functional connectivity between left anterior insula and left cerebellum. Our findings show that individual differences in ES are associated with differential anterior insula responses to primary sensory (flavor) stimuli as well as to intrinsic functional cortico-cerebellar connectivity, the latter suggesting a basis in the brain intrinsic functional architecture of the regulation of emotional experiences.

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.