The role of ACC in Anosognosia: a TMS study.

Transcranial Magnetic Stimulation (TMS) is a technic wich allows Neuroscience researchers to disrupt or improve the normal brain activity in a strategic and focalized cortical areas. Our present work using TMS is focused on research the role of Anterior Cingolate Cortex (ACC) to discover its causal implications over autoreferencial judgments of own behaviour using healthy controls.If our hypothesis is confirmed and ACC has a keyrole in those autoreferential judgements; new research lines and stimulation techniques could strenghten to improve quality of life and feelings of overcoming to thousands of mental health patients and neurodegenerative.

Impact of cannabis inhalation on driving skills in occasional smokers

Objectives: Our aim was to study the brain regions involved in a divided attention tracking task related to driving in occasional cannabis smokers. In addition we assessed the relationship between THC levels in whole blood and changes in brain activity, behavioural and psychomotor performances. Methods: Twenty-one smokers participated to two independent cross-over fMRI experiments before and after smoking cannabis and a placebo. The paradigm was based on a visuo-motor tracking task, alternating active tracking blocks with passive tracking viewing and rest condition. Half of the active tracking conditions included randomly presented traffic lights as distractors. Blood samples were taken at regular intervals to determine the time-profiles of the major cannabinoids. Their levels during the fMRI experiments were interpolated from concentrations measured by GCMS/ MS just before and after brain imaging. Results: Behavioural data, such as the discard between target and cursor, the time of correct tracking and the reaction time during traffic lights appearance showed a statistical significant impairment of subject s skills due to THC intoxication. Highest THC blood concentrations were measured soon after smoking and ranged between 28.8 and 167.9 ng/ml. These concentrations reached values of a few ng/ml during the fMRI. fMRI results pointed out that under the effect of THC, high order visual areas (V3d) and Intraparietal sulcus (IPS) showed an higher activation compared to the control condition. The opposite comparison showed a decrease of activation during the THC condition in the anterior cingulate gyrus and orbitofrontal areas. In these locations, the BOLD showed a negative correlation with the THC level. Conclusion: Acute cannabis smoking significantly impairs performances and brain activity during active tracking tasks, partly reorganizing the recruitment of brain areas of the attention network. Neural activity in the anterior cingulate might be responsible of the changes in the cognitive controls required in our divided attention task.

In-vivo magnetic resonance imaging of the structural core of the Papez circuit in humans.

Papez circuit is one of the major pathways of the limbic system, and it is involved in the control of memory and emotion. Structural and functional alterations have been reported in psychiatric, neurodegenerative, and epileptic diseases. Despite the clinical interest, however, in-vivo imaging of the entire circuit remains a technological challenge. We used magnetic resonance diffusion spectrum imaging to comprehensively picture the Papez circuit in healthy humans: (i) the hippocampus-mammillary body pathway, (ii) the connections between the lateral subiculum and the cingulate cortex, and (iii) the mammillo-thalamic tract. The diagnostic and therapeutic implications of these results are discussed in the context of recent findings reporting the involvement of the Papez circuit in neurological and psychiatric diseases.

The brain uses single-trial multisensory memories to discriminate without awareness.

Multisensory experiences enhance perceptions and facilitate memory retrieval processes, even when only unisensory information is available for accessing such memories. Using fMRI, we identified human brain regions involved in discriminating visual stimuli according to past multisensory vs. unisensory experiences. Subjects performed a completely orthogonal task, discriminating repeated from initial image presentations intermixed within a continuous recognition task. Half of initial presentations were multisensory, and all repetitions were exclusively visual. Despite only single-trial exposures to initial image presentations, accuracy in indicating image repetitions was significantly improved by past auditory-visual multisensory experiences over images only encountered visually. Similarly, regions within the lateral-occipital complex-areas typically associated with visual object recognition processes-were more active to visual stimuli with multisensory than unisensory pasts. Additional differential responses were observed in the anterior cingulate and frontal cortices. Multisensory experiences are registered by the brain even when of no immediate behavioral relevance and can be used to categorize memories. These data reveal the functional efficacy of multisensory processing.

Altered brain mechanisms of emotion processing in pre-manifest Huntington's disease.

Huntington's disease is an inherited neurodegenerative disease that causes motor, cognitive and psychiatric impairment, including an early decline in ability to recognize emotional states in others. The pathophysiology underlying the earliest manifestations of the disease is not fully understood; the objective of our study was to clarify this. We used functional magnetic resonance imaging to investigate changes in brain mechanisms of emotion recognition in pre-manifest carriers of the abnormal Huntington's disease gene (subjects with pre-manifest Huntington's disease): 16 subjects with pre-manifest Huntington's disease and 14 control subjects underwent 1.5 tesla magnetic resonance scanning while viewing pictures of facial expressions from the Ekman and Friesen series. Disgust, anger and happiness were chosen as emotions of interest. Disgust is the emotion in which recognition deficits have most commonly been detected in Huntington's disease; anger is the emotion in which impaired recognition was detected in the largest behavioural study of emotion recognition in pre-manifest Huntington's disease to date; and happiness is a positive emotion to contrast with disgust and anger. Ekman facial expressions were also used to quantify emotion recognition accuracy outside the scanner and structural magnetic resonance imaging with voxel-based morphometry was used to assess the relationship between emotion recognition accuracy and regional grey matter volume. Emotion processing in pre-manifest Huntington's disease was associated with reduced neural activity for all three emotions in partially separable functional networks. Furthermore, the Huntington's disease-associated modulation of disgust and happiness processing was negatively correlated with genetic markers of pre-manifest disease progression in distributed, largely extrastriatal networks. The modulated disgust network included insulae, cingulate cortices, pre- and postcentral gyri, precunei, cunei, bilateral putamena, right pallidum, right thalamus, cerebellum, middle frontal, middle occipital, right superior and left inferior temporal gyri, and left superior parietal lobule. The modulated happiness network included postcentral gyri, left caudate, right cingulate cortex, right superior and inferior parietal lobules, and right superior frontal, middle temporal, middle occipital and precentral gyri. These effects were not driven merely by striatal dysfunction. We did not find equivalent associations between brain structure and emotion recognition, and the pre-manifest Huntington's disease cohort did not have a behavioural deficit in out-of-scanner emotion recognition relative to controls. In addition, we found increased neural activity in the pre-manifest subjects in response to all three emotions in frontal regions, predominantly in the middle frontal gyri. Overall, these findings suggest that pathophysiological effects of Huntington's disease may precede the development of overt clinical symptoms and detectable cerebral atrophy.

Mental imagery for full and upper human bodies: common right hemisphere activations and distinct extrastriate activations.

The processing of human bodies is important in social life and for the recognition of another person's actions, moods, and intentions. Recent neuroimaging studies on mental imagery of human body parts suggest that the left hemisphere is dominant in body processing. However, studies on mental imagery of full human bodies reported stronger right hemisphere or bilateral activations. Here, we measured functional magnetic resonance imaging during mental imagery of bilateral partial (upper) and full bodies. Results show that, independently of whether a full or upper body is processed, the right hemisphere (temporo-parietal cortex, anterior parietal cortex, premotor cortex, bilateral superior parietal cortex) is mainly involved in mental imagery of full or partial human bodies. However, distinct activations were found in extrastriate cortex for partial bodies (right fusiform face area) and full bodies (left extrastriate body area). We propose that a common brain network, mainly on the right side, is involved in the mental imagery of human bodies, while two distinct brain areas in extrastriate cortex code for mental imagery of full and upper bodies.

Schizotypal perceptual aberrations of time: correlation between score, behavior and brain activity.

A fundamental trait of the human self is its continuum experience of space and time. Perceptual aberrations of this spatial and temporal continuity is a major characteristic of schizophrenia spectrum disturbances--including schizophrenia, schizotypal personality disorder and schizotypy. We have previously found the classical Perceptual Aberration Scale (PAS) scores, related to body and space, to be positively correlated with both behavior and temporo-parietal activation in healthy participants performing a task involving self-projection in space. However, not much is known about the relationship between temporal perceptual aberration, behavior and brain activity. To this aim, we composed a temporal Perceptual Aberration Scale (tPAS) similar to the traditional PAS. Testing on 170 participants suggested similar performance for PAS and tPAS. We then correlated tPAS and PAS scores to participants' performance and neural activity in a task of self-projection in time. tPAS scores correlated positively with reaction times across task conditions, as did PAS scores. Evoked potential mapping and electrical neuroimaging showed self-projection in time to recruit a network of brain regions at the left anterior temporal cortex, right temporo-parietal junction, and occipito-temporal cortex, and duration of activation in this network positively correlated with tPAS and PAS scores. These data demonstrate that schizotypal perceptual aberrations of both time and space, as reflected by tPAS and PAS scores, are positively correlated with performance and brain activation during self-projection in time in healthy individuals along the schizophrenia spectrum.

Neural substrates of social emotion regulation: a FMRI study on imitation and expressive suppression to dynamic facial signals.

Emotion regulation is crucial for successfully engaging in social interactions. Yet, little is known about the neural mechanisms controlling behavioral responses to emotional expressions perceived in the face of other people, which constitute a key element of interpersonal communication. Here, we investigated brain systems involved in social emotion perception and regulation, using functional magnetic resonance imaging (fMRI) in 20 healthy participants. The latter saw dynamic facial expressions of either happiness or sadness, and were asked to either imitate the expression or to suppress any expression on their own face (in addition to a gender judgment control task). fMRI results revealed higher activity in regions associated with emotion (e.g., the insula), motor function (e.g., motor cortex), and theory of mind (e.g., [pre]cuneus) during imitation. Activity in dorsal cingulate cortex was also increased during imitation, possibly reflecting greater action monitoring or conflict with own feeling states. In addition, premotor regions were more strongly activated during both imitation and suppression, suggesting a recruitment of motor control for both the production and inhibition of emotion expressions. Expressive suppression (eSUP) produced increases in dorsolateral and lateral prefrontal cortex typically related to cognitive control. These results suggest that voluntary imitation and eSUP modulate brain responses to emotional signals perceived from faces, by up- and down-regulating activity in distributed subcortical and cortical networks that are particularly involved in emotion, action monitoring, and cognitive control.

An fMRI Study of Emotional engagement in decicion-making

It has been suggested that decisionmaking depends on sensitive feelings associatedwith cognitive processing rather than cognitiveprocessing alone. From human lesions, we knowthe medial anterior inferior-ventral prefrontalcortex processes the sensitivity associated withcognitive processing, it being essentiallyresponsible for decision making.In this fMRI (functional Magnetic ResonanceImage) study 15 subjects were analyzed usingmoral dilemmas as probes to investigate the neuralbasis for painful-emotional sensitivity associatedwith decision making. We found that a networkcomprising the posterior and anterior cingulateand the medial anterior prefrontal cortex wassignificantly and specifically activated by painfulmoral dilemmas, but not by non-painful dilemmas.These findings provide new evidence that thecingulate and medial anterior prefrontal areinvolved in processing painful emotionalsensibility, in particular, when decision makingtakes place. We speculate that decision makinghas a cognitive component processed by cognitivebrain areas and a sensitivity component processedby emotional brain areas. The structures activatedsuggest that decision making depends on painfulemotional feeling processing rather than cognitiveprocessing when painful feeling processinghappens

Brain Dopamine and Serotonin Receptors in the Perception of Pain. Positron Emission Tomography Studies in Healthy Subjects

The role of dopamine and serotonin in spinal pain regulation is well established. However, little is known concerning the role of brain dopamine and serotonin in the perception of pain in humans. The aim of this study was to assess the potential role of brain dopamine and serotonin in determining experimental pain sensitivity in humans using positron emission tomography (PET) and psychophysical methods. A total of 39 healthy subjects participated in the study, and PET imaging was performed to assess brain dopamine D2/D3 and serotonin 5-HT_1A receptor availability. In a separate session, sensitivity to pain and touch was assessed with traditional psychophysical methods, allowing the evaluation of potential associations between D2/D3 and 5-HT_1A binding and psychophysical responses. The subjects’ responses were also analyzed according to Signal Detection Theory, which enables separate assessment of the subject’s discriminative capacity (sensory factor) and response criterion (non-sensory factor). The study found that the D2/D3 receptor binding in the right putamen was inversely correlated with pain threshold and response criterion. 5-HT_1A binding in cingulate cortex, inferior temporal gyrus and medial prefrontal cortex was inversely correlated with discriminative capacity for touch. Additionally, the response criterion for pain and intensity rating of suprathreshold pain were inversely correlated with 5-HT_1A binding in multiple brain areas. The results suggest that brain D2/D3 receptors and 5-HT_1A receptors modulate sensitivity to pain and that the pain modulatory effects may, at least partly, be attributed to influences on the response criterion. 5-HT_1A receptors are also involved in the regulation of touch by having an effect on discriminative capacity.

Verbal learning in mild cognitive impairment and alzheimer's disease : behavioural and neural approaches

The main focus of the present thesis was at verbal episodic memory processes that are particularly vulnerable to preclinical and clinical Alzheimer’s disease (AD). Here these processes were studied by a word learning paradigm, cutting across the domains of memory and language learning studies. Moreover, the differentiation between normal aging, mild cognitive impairment (MCI) and AD was studied by the cognitive screening test CERAD. In study I, the aim was to examine how patients with amnestic MCI differ from healthy controls in the different CERAD subtests. Also, the sensitivity and specificity of the CERAD screening test to MCI and AD was examined, as previous studies on the sensitivity and specificity of the CERAD have not included MCI patients. The results indicated that MCI is characterized by an encoding deficit, as shown by the overall worse performance on the CERAD Wordlist learning test compared with controls. As a screening test, CERAD was not very sensitive to MCI. In study II, verbal learning and forgetting in amnestic MCI, AD and healthy elderly controls was investigated with an experimental word learning paradigm, where names of 40 unfamiliar objects (mainly archaic tools) were trained with or without semantic support. The object names were trained during a 4-day long period and a follow-up was conducted one week, 4 weeks and 8 weeks after the training period. Manipulation of semantic support was included in the paradigm because it was hypothesized that semantic support might have some beneficial effects in the present learning task especially for the MCI group, as semantic memory is quite well preserved in MCI in contrast to episodic memory. We found that word learning was significantly impaired in MCI and AD patients, whereas forgetting patterns were similar across groups. Semantic support showed a beneficial effect on object name retrieval in the MCI group 8 weeks after training, indicating that the MCI patients’ preserved semantic memory abilities compensated for their impaired episodic memory. The MCI group performed equally well as the controls in the tasks tapping incidental learning and recognition memory, whereas the AD group showed impairment. Both the MCI and the AD group benefited less from phonological cueing than the controls. Our findings indicate that acquisition is compromised in both MCI and AD, whereas long13 term retention is not affected to the same extent. Incidental learning and recognition memory seem to be well preserved in MCI. In studies III and IV, the neural correlates of naming newly learned objects were examined in healthy elderly subjects and in amnestic MCI patients by means of positron emission tomography (PET) right after the training period. The naming of newly learned objects by healthy elderly subjects recruited a left-lateralized network, including frontotemporal regions and the cerebellum, which was more extensive than the one related to the naming of familiar objects (study III). Semantic support showed no effects on the PET results for the healthy subjects. The observed activation increases may reflect lexicalsemantic and lexical-phonological retrieval, as well as more general associative memory mechanisms. In study IV, compared to the controls, the MCI patients showed increased anterior cingulate activation when naming newly learned objects that had been learned without semantic support. This suggests a recruitment of additional executive and attentional resources in the MCI group.

Anatomical connections of the periaqueductal gray: specific neural substrates for different kinds of fear

The periaqueductal gray (PAG) has been traditionally considered to be an exit relay for defensive responses. Functional mapping of its subdivisions has advanced our knowledge of this structure, but synthesis remains difficult mainly because results from lesion and stimulation studies have not correlated perfectly. After using a strategy that combined both techniques and a reevaluation of the available literature on PAG function and connections, we propose here that freezing could be mediated by different PAG subdivisions depending on the presence of immediate danger or exposure to related signaling cues. These subdivisions are separate functional entities with distinct descending and ascending connections that are likely to play a role in different defensive responses. The existence of ascending connections also suggests that the PAG is not simply a final common path for defensive responses. For example, the possibility that indirect ascending connections to the cingulate cortex could play a role in the expression of freezing evoked by activation of the neural substrate of fear in the dorsal PAG has been considered.

Dexamethasone-induced reactivation of bovine herpesvirus type 5 latent infection in experimentally infected rabbits results in a broader distribution of latent viral DNA in the brain

Bovine herpesvirus type 5 (BHV-5) is a major agent of meningoencephalitis in cattle and establishes latent infections mainly in sensory nerve ganglia. The distribution of latent BHV-5 DNA in the brain of rabbits prior to and after virus reactivation was studied using a nested PCR. Fifteen rabbits inoculated intranasally with BHV-5 were euthanized 60 days post-inoculation (group A, N = 8) or submitted to dexamethasone treatment (2.6 mg kg-1 day-1, im, for 5 days) and euthanized 60 days later (group B, N = 7) for tissue examination. Two groups of BHV-1-infected rabbits (C, N = 3 and D, N = 3) submitted to each treatment were used as controls. Viral DNA of group A rabbits was consistently detected in trigeminal ganglia (8/8), frequently in cerebellum (5/8), anterior cerebral cortex and pons-medulla (3/8) and occasionally in dorsolateral (2/8), ventrolateral and posterior cerebral cortices, midbrain and thalamus (1/8). Viral DNA of group B rabbits showed a broader distribution, being detected at higher frequency in ventrolateral (6/7) and posterior cerebral cortices (5/7), pons-medulla (6/7), thalamus (4/7), and midbrain (3/7). In contrast, rabbits inoculated with BHV-1 harbored viral DNA almost completely restricted to trigeminal ganglia and the distribution did not change post-reactivation. These results demonstrate that latency by BHV-5 is established in several areas of the rabbit's brain and that virus reactivation leads to a broader distribution of latent viral DNA. Spread of virus from trigeminal ganglia and other areas of the brain likely contributes to this dissemination and may contribute to the recrudescence of neurological disease frequently observed upon BHV-5 reactivation.

Autonomic prediction of error-related ERP components in perceptual and conceptual tasks in older and younger adults

In studies of cognitive processing, the allocation of attention has been consistently linked to subtle, phasic adjustments in autonomic control. Both autonomic control of heart rate and control of the allocation of attention are known to decline with age. It is not known, however, whether characteristic individual differences in autonomic control and the ability to control attention are closely linked. To test this, a measure of parasympathetic function, vagal tone (VT) was computed from cardiac recordings from older and younger adults taken before and during performance of two attentiondemanding tasks - the Eriksen visual flanker task and the source memory task. Both tasks elicited event-related potentials (ERPs) that accompany errors, i.e., error-related negativities (ERNs) and error positivities (Pe's). The ERN is a negative deflection in the ERP signal, time-locked to responses made on incorrect trials, likely generated in the anterior cingulate. It is followed immediately by the Pe, a broad, positive deflection which may reflect conscious awareness of having committed an error. Age-attenuation ofERN amplitude has previously been found in paradigms with simple stimulus-response mappings, such as the flanker task, but has rarely been examined in more complex, conceptual tasks. Until now, there have been no reports of its being investigated in a source monitoring task. Age-attenuation of the ERN component was observed in both tasks. Results also indicated that the ERNs generated in these two tasks were generally comparable for young adults. For older adults, however, the ERN from the source monitoring task was not only shallower, but incorporated more frontal processing, apparently reflecting task demands. The error positivities elicited by 3 the two tasks were not comparable, however, and age-attenuation of the Pe was seen only in the more perceptual flanker task. For younger adults, it was Pe scalp topography that seemed to reflect task demands, being maximal over central parietal areas in the flanker task, but over very frontal areas in the source monitoring task. With respect to vagal tone, in the flanker task, neither the number of errors nor ERP amplitudes were predicted by baseline or on-task vagal tone measures. However, in the more difficult source memory task, lower VT was marginally associated with greater numbers of source memory errors in the older group. Thus, for older adults, relatively low levels of parasympathetic control over cardiac response coincided with poorer source memory discrimination. In both groups, lower levels of baseline VT were associated with larger amplitude ERNs, and smaller amplitude Pe's. Thus, low VT was associated in a conceptual task with a greater "emergency response" to errors, and at the same time, reduced awareness of having made them. The efficiency of an individual's complex cognitive processing was therefore associated with the flexibility of parasympathetic control of heart rate, in response to a cognitively challenging task.

Effect of mindfulness meditation on the neural substrates of emotion processing and resting state in experienced and beginner meditators

La méditation par le ‘mindfulness’ favorise la stabilité émotionelle, mais les mécanismes neuroneux qui sous-tendent ces effets sont peu connus. Ce projet investiga l’effet du ‘mindfulness’ sur les réponses cérébrales et subjectives à des images négatives, positives et neutres chez des méditants expérimentés et des débutants au moyen de l’imagerie par résonance magnétique fonctionnelle (IRMf). Le ‘mindfulness’ atténua l’intensité émotionelle via différents mécanismes cérébraux pour chaque groupe. Comparés aux méditants, les débutants manifestèrent une déactivation de l’amygdale en réponse aux stimuli émotifs durant le ‘mindfulness’. Comparés aux débutants, les méditants exhibèrent une déactivation de régions du réseau du mode par défaut (RMD) pendant le ‘mindfulness’ pour tous stimuli (cortex médian préfrontal [CMP], cortex cingulaire postérieur [CCP]). Le RMD est constitué de régions fonctionnellement connectées, activées au repos et déactivées lors de tâches explicites. Cependant, nous ne connaissons pas les impacts de l’entraînement par la méditation sur la connectivité entre régions du RMD et si ces effets persistent au-delà d’un état méditatif. La connectivité fonctionnelle entre régions du RMD chez les méditants et débutants au repos fut investiguée au moyen de l’IRMf. Comparés aux débutants, les méditants montrèrent une connectivité affaiblie entre subdivisions du CMP, et une connectivité accrue entre le lobule pariétal inférieur et trois regions du RMD. Ces résultats reflètent que les bienfaits immédiats du ‘mindfulness’ sur la psychopathologie pourraient être dûs à une déactivation de régions limbiques impliquées dans la réactivité émotionelle. De plus, les bienfaits à long-terme de la méditation sur la stabilité émotionelle pourrait être dûs à une déactivation de régions corticales et cingulaires impliquées dans l’évaluation de la signification émotive et une connectivité altérée entre régions du RMD à l’état de repos.