Marcella Brunetti

Human brain activation during passive listening to sounds from different locations: An fMRI and MEG study

Recent animal and human studies indicate the existence of a neural pathway for sound localization, which is similar to the “where” pathway of the visual system and distinct from the sound identification pathway. This study sought to highlight this pathway using a passive listening protocol. We employed fMRI to study cortical areas, activated during the processing of sounds coming from different locations, and MEG to disclose the temporal dynamics of these areas. In addition, the hypothesis of different activation levels in the right and in the left hemispheres, due to hemispheric specialization of the human brain, was investigated. The fMRI results indicate that the processing of sound, coming from different locations, activates a complex neuronal circuit, similar to the sound localization system described in monkeys known as the auditory “where” pathway. This system includes Heschls gyrus, the superior temporal gyrus, the supramarginal gyrus, and the inferior and middle frontal lobe. The MEG analysis allowed assessment of the timing of this circuit: the activation of Heschls gyrus was observed 139 ms after the auditory stimulus, the peak latency of the source located in the superior temporal gyrus was at 156 ms, and the inferior parietal lobule and the supramarginal gyrus peaked at 162 ms. Both hemispheres were found to be involved in the processing of sounds coming from different locations, but a stronger activation was observed in the right hemisphere. Hum. Brain Mapping, 2005.

ELEVATED RESPONSE OF HUMAN AMYGDALA TO NEUTRAL STIMULI IN MILD POST TRAUMATIC STRESS DISORDER: NEURAL CORRELATES OF GENERALIZED EMOTIONAL RESPONSE

Previous evidence from functional magnetic resonance imaging (fMRI) studies has shown that amygdala responses to emotionally neutral pictures are exaggerated at a group level in patients with severe post-traumatic stress disorder (PTSD) [Hendler T, Rotshtein P, Yeshurun Y, Weizmann T, Kahn I, Ben-Bashat D, Malach R, Bleich A (2003) Neuroimage 19(3):587-600]. The present fMRI study tested the hypothesis that amygdala responses are elevated not only in response to negative pictures but also to neutral pictures as a function of disease severity in patients with mild symptoms and in subjects who did not develop symptoms. To this end, fMRI scans were performed in 10 patients with mild PTSD and 10 healthy controls (both victims of a bank robbery), during the execution of a visuo-attentional task in which they were asked to observe emotionally negative or neutral pictures. Control subjects showed enhanced amygdala responses to emotionally negative stimuli compared to neutral stimuli. On the contrary, PTSD patients were characterized by high amygdala responses to both neutral and emotional pictures, with no statistically significant difference between the two classes of stimuli. In the entire group, we found correlations among the severity of the PTSD symptoms, task performance, and amygdala activation during the processing of neutral stimuli. Results of this study suggest that amygdala responses and the selectivity of the emotional response to neutral stimuli are elevated as a function of disease severity in PTSD patients with mild symptoms.

BDNF serum levels in subjects developing or not post-traumatic stress disorder after trauma exposure

Post-traumatic stress disorder (PTSD) is a syndrome resulting from exposure to a severe traumatic event that poses threatened death or injury and produces intense fear and helplessness. The neural structures implicated in PTSD development belong to the limbic system, an important region for emotional processing. Brain-derived neurotrophic factor (BDNF) is a neurotrophin that serves as survival factor for selected populations of central nervous system (CNS) neurons and plays a role in the limbic system by regulating synaptic plasticity, memory processes and behavior. Impaired BDNF production in the brain can lead to a variety of CNS dysfunctions including symptoms associated with PTSD. However, so far fewer studies have investigated this neurotrophin in patients with PTSD. Furthermore, given the multiple role of BDNF in various CNS disorders, it cannot be excluded that traumatic events per se may influence neurotrophin levels, without a direct association to the PTSD syndrome. To elucidate these issues, in this study we analyzed BDNF serum levels in two groups of subjects: patients with trauma exposure who developed PTSD, and subjects with trauma exposure who did not develop PTSD. We found that BDNF serum levels were lower in PTSD patients as compared to related control subjects. Thus, these data suggest that BDNF might be involved in pathophysiology of PTSD and consequently therapeutic approaches aimed at restoring BDNF serum levels may be beneficial to this pathology.

Hypothalamus, sexual arousal and psychosexual identity in human males: a functional magnetic resonance imaging study.

In a recent functional magnetic resonance imaging study, a complex neural circuit was shown to be involved in human males during sexual arousal [A. Ferretti et al. (2005) Neuroimage, 26, 1086]. At group level, there was a specific correlation between penile erection and activations in anterior cingulate, insula, amygdala, hypothalamus and secondary somatosensory regions. However, it is well known that there are remarkable inter‐individual differences in the psychological view and attitude to sex of human males. Therefore, a crucial issue is the relationship among cerebral responses, sexual arousal and psychosexual identity at individual level. To address this issue, 18 healthy male subjects were recruited. Their deep sexual identity (DSI) was assessed following the construct revalidation by M. Olivetti Belardinelli [(1994) Sci. Contrib. Gen. Psychol., 11, 131] of the Franck drawing completion test, a projective test providing, according to this revalidation, quantitative scores on ‘accordance/non‐accordance’ between self‐reported and psychological sexual identity. Cerebral activity was evaluated by means of functional magnetic resonance imaging during hard‐core erotic movies and sport movies. Results showed a statistically significant positive correlation between the blood oxygen level‐dependent signal in bilateral hypothalamus and the Franck drawing completion test score during erotic movies. The higher the blood oxygen level‐dependent activation in bilateral hypothalamus, the higher the male DSI profile. These results suggest that, in male subjects, inter‐individual differences in the DSI are strongly correlated with blood flow to the bilateral hypothalamus, a dimorphic brain region deeply implicated in instinctual drives including reproduction.

Thermal signature of fear conditioning in mild post traumatic stress disorder.

Fear conditioning has been proposed as an important factor involved in the etiology of posttraumatic stress disorder (PTSD). We examined fear processing in PTSD patients with mild symptoms and in individuals who did not develop symptoms (both groups consisting of victims of a bank robbery), through the study of fear-conditioned response. Conditioned responses were quantified by the skin conductance response (SCR) and the facial thermal response, the latter being measured by high-resolution functional thermal infrared (fIR) imaging. We found: (a) a change of the physiological parameters with respect to the baseline condition in both control subjects and PTSD patients during the conditioning phase; (b) the permanence of the conditioning effect in the maintenance phase in both control and PTSD patients; (c) patients and controls did differ for the variation across the phases of the physiological parameters rather than for their absolute values, showing that PTSD patients had a prolonged excitation and higher tonic component of autonomic activity. These results, although preliminary, indicate that the analysis of SCR and facial thermal response during the conditioning paradigm is a promising psychometric method of investigation, even in the case of low level of PTSD symptom severity. To the best of our knowledge, this study is the first attempt to discriminate between control subjects and PTSD patients with mild symptoms through infrared thermal imaging. It may suggest feasible approaches for diagnostic screening in the early phases of the disorder and in the assessment of preventive measures and therapies.

Pharmacological Treatments in Gambling Disorder: A Qualitative Review

Gambling disorder (GD) is a psychiatric condition associated with both social and family costs; DSM-5 currently includes GD among addictive disorders. Despite the high burden of this condition, to date there are no treatment guidelines approved by Food and Drug Administration (FDA). Purpose of this paper is to offer a qualitative overview about the different pharmacologic agents used for the treatment of GD. Our analysis, conducted on a final selection of 75 scientific papers, demonstrates that a variety of pharmaceutical classes have been utilised, with different results. Published data, although limited by brief duration of the studies and small number of enrolled subjects, shows mixed evidence for serotonergic antidepressants, opioid antagonists, and mood stabilizers. Other compounds, such as glutamatergic agents and psychostimulants, deserve further studies.

Do You Know What I Mean? Brain Oscillations and the Understanding of Communicative Intentions

Pointing gesture allows children to communicate their intentions before the acquisition of language. In particular, two main purposes seem to underlie the gesture: to request a desired object (imperative pointing) or to share attention on that object (declarative pointing). Since the imperative pointing has an instrumental goal and the declarative has an interpersonal one, only the latter gesture is thought to signal the infant’s awareness of the communicative partner as a mental agent. The present study examined the neural responses of adult subjects with the aim to test the hypothesis that declarative rather than imperative pointing reflects mentalizing skills. Fourteen subjects were measured in a magnetoencephalographic environment including four conditions, based on the goal of the pointing – imperative or declarative – and the role of the subject – sender or receiver of pointing. Time–frequency modulations of brain activity in each condition (declarative production and comprehension, imperative production and comprehension) were analyzed. Both low beta and high beta power were stronger during declarative than imperative condition in anterior cingulated cortex and right posterior superior temporal sulcus, respectively. Furthermore, high gamma activity was higher in right temporo-parietal junction during the sender than receiving condition. This suggests that communicative pointing modulated brain regions previously described in neuroimaging research as linked to social cognitive skills and that declarative pointing is more capable of eliciting that activation than imperative. Our results contribute to the understanding of the roles of brain rhythm dynamics in social cognition, thus supporting neural research on that topic during developmental both in typical and atypical conditions, such as autism spectrum disorder. In particular, the identification of relevant regions in a mature brain may stimulate a future work on the developmental changes of neural activation in the same regions.

BDNF concentration and impulsiveness level in post-traumatic stress disorder

Among the symptoms of post-traumatic stress disorder (PTSD), impulsiveness has been observed in patients with high levels of hyperarousal. Recent literature reveals the importance of investigating the role of neurotrophins, such as brain-derived neurotrophic factor (BDNF), in several psychiatric disorders. Specifically, contrasting findings have been reported on the levels of serum BDNF in subjects with PTSD. The aim of the present study was to investigate the correlation between BDNF serum levels and impulsiveness in PTSD. To this end, we measured BDNF serum levels in 23 PTSD patients and a control group of 19 trauma-exposed non-PTSD subjects. Results indicate a positive correlation in the PTSD group; that is, the higher the BDNF levels the higher the impulsiveness score, as measured by the Barratt Impulsiveness Scale (BIS-11), suggesting that impulsiveness could be associated with greater BDNF production. Alternatively, it is also possible that high impulsiveness acts as a psychological mechanism that counteracts the negative effects exerted by the traumatic experience and the associated obsessive thoughts. The present paper discusses both hypotheses.

Framing deductive reasoning with emotional content: An fMRI study

In the literature concerning the study of emotional effect on cognition, several researches highlight the mechanisms of reasoning ability and the influence of emotions on this ability. However, up to now, no neuroimaging study was specifically devised to directly compare the influence on reasoning performance of visual task-unrelated with semantic task-related emotional information. In the present functional fMRI study, we devised a novel paradigm in which emotionally negative vs. neutral visual stimuli (context) were used as primes, followed by syllogisms composed of propositions with emotionally negative vs. neutral contents respectively. Participants, in the MR scanner, were asked to assess the logical validity of the syllogisms. We have therefore manipulated the emotional state and arousal induced by the visual prime as well as the emotional interference exerted by the syllogism content. fMRI data indicated a medial prefrontal cortex deactivation and lateral/dorsolateral prefrontal cortex activation in conditions with negative context. Furthermore, a lateral/dorsolateral prefrontal cortex modulation caused by syllogism content was observed. Finally, behavioral data confirmed the influence of emotional task-related stimuli on reasoning ability, since the performance was worse in conditions with syllogisms involving negative emotions. Therefore, on the basis of these data, we conclude that emotional states can impair the performance in reasoning tasks by means of the delayed general reactivity, whereas the emotional content of the target may require a larger amount of top-down resources to be processed.

Response inhibition failure to visual stimuli paired with a “single-type” stressor in PTSD patients: An fMRI pilot study

Patients with post-traumatic stress disorder (PTSD) tend to misinterpret innocuous stimuli as potential threats, possibly due to a conditioning provoked by traumatic episodes. Previous neuroimaging evidence has shown an abnormal activation of the amygdala and prefrontal cortex in PTSD patients during fear conditioning and extinction. Nevertheless, the effects of a single-type adverse stressor on that circuit remain poorly explored. We tested the hypothesis that a single-type adverse episode is able to affect the prefrontal cortex and amygdala response to conditioned stimuli. To test this hypothesis, fMRI recordings were performed in PTSD patients and trauma-exposed controls during the observation of neutral and negative paired or non-paired pictures with an adverse stimulus by means of a single association. Results showed that left amygdala activation during negative reinforced stimuli was correlated with the score of PTSD clinical scale across all subjects. Furthermore, in the traumatized non-PTSD group, the activation of the dorso-medial prefrontal cortex and bilateral amygdala was lower during the observation of the reinforced (CS(+)) versus non-reinforced pictures (CS(-)) in response to emotionally negative stimuli. This was not the case in the PTSD patients. These results suggest that in PTSD patients, a single-episode conditioning unveils the failure of an inhibitory mechanism moderating the activity of the prefrontal cortex and amygdala in response to adverse and neutral stimuli.