Hierarchical models have been proposed to explain how the brain encodes actions, whereby different areas represent different features, such as gesture kinematics, target object, action goal, and meaning. The visual processing of action-related information is distributed over a well-known network of brain regions spanning separate anatomical areas, attuned to specific stimulus properties, and referred to as action observation network (AON). To determine the brain organization of these features, we measured representational geometries during the observation of a large set of transitive and intransitive gestures in two independent functional magnetic resonance imaging experiments. We provided evidence for a partial dissociation between kinematics, object characteristics, and action meaning in the occipito-parietal, ventro-temporal, and lateral occipito-temporal cortex, respectively. Importantly, most of the AON showed low specificity to all the explored features, and representational spaces sharing similar information content were spread across the cortex without being anatomically adjacent. Overall, our results support the notion that the AON relies on overlapping and distributed coding and may act as a unique representational space instead of mapping features in a modular and segregated manner.

Although economic decision-making is commonly characterized as a purely rational phenomenon, it is clear that real-world decision-making is influenced by emotions. Yet, relatively little is known about the neural correlates of this process. To explore this issue, 20 participants underwent fMRI scanning while engaged in the Prisoner's Dilemma game under partner-directed sympathy, anger and neutral emotion conditions. Participants were most and least likely to cooperate after sympathy and anger induction, respectively, with the neutral condition eliciting intermediate cooperation rates. Moreover, the sympathy condition elicited quicker responses for cooperation than defection choices, whereas this pattern was reversed in the anger and neutral conditions. Left amygdala activation showed a positive correlation with cooperation rates and self-reports of partner directed sympathy in the sympathy condition. In the anger condition, left putamen activation was positively correlated with cooperation rates and negatively correlated with self-reports of partner directed anger strength. These findings indicate that while the left amygdala activation may be indicative of emotion enhancement and increase of cooperative behavior, the left putamen may help to suppress an emotion to overcome anger and engage in cooperation.

This is the first study to examine functional brain activation in a single case of Highly Superior Autobiographical Memory (HSAM) who shows no sign of obsessive compulsive disorder (OCD). While previous work has documented the existence of HSAM, information about brain areas involved in this exceptional form of memory for personal events relies on structural and resting state connectivity data, with mixed results so far. In this first task-based functional magnetic resonance Imaging (fMRI) study of a normal individual with HSAM, dates were presented as cues and two phases were assessed during memory retrieval, initial access and later elaboration. Results showed that initial access was very fast, did not activate the hippocampus, and involved activation of predominantly posterior visual areas, including the precuneus. These areas typically become active during later stages of elaboration of personal memories rather than during initial access. Elaboration involved a balanced bilateral activation of most of the autobiographical network areas, rather than the more typical shifts observed in people without HSAM. Overall, the pattern of brain activations, which rests on repeated observations in a single individual, highlights a strong involvement of the precuneus and an idiosyncratic initial access to personal memory representations. Implications for the nature of personal memories in HSAM are discussed.

There are cognitive domains which remain fully functional in a proportion of Alzheimer's disease (AD) patients. It is unknown, however, what distinctive mechanisms sustain such efficient processing. The concept of "cognitive efficiency" was investigated in these patients by operationalizing it as a function of the level of performance shown on the Letter Fluency test, on which, very often, patients in the early stages of AD show unimpaired performance. Forty-five individuals at the prodromal/early stage of AD (diagnosis supported by subsequent clinical follow-ups) and 45 healthy controls completed a battery of neuropsychological tests and an MRI protocol which included resting state acquisitions. The Letter Fluency test was the only task on which no between-group difference in performance was found. Participants were divided into "low-performing" and "high-performing" according to the global median. Dual-regression methods were implemented to compute six patterns of network connectivity. The diagnosis-by-level of performance interaction was inferred on each pattern to determine the network distinctiveness of efficient performance in AD. Significant interactions were found in the anterior default mode network, and in both left and right executive control networks. For all three circuits, high-performing patients showed increased connectivity within the ventral and dorsal part of BA19, as confirmed by post hoc t tests. Peristriate remapping is suggested to play a compensatory role. Since the occipital lobe is the neurophysiological source of long-range cortical connectivity, it is speculated that the physiological mechanisms of functional connectivity might sustain occipital functional remapping in early AD, particularly for those functions which are sustained by areas not excessively affected by the prodromal disease.

Mental effort is a common phenomenological construct deeply linked to volition and self-control. While it is often assumed that the amount of exertion invested in a task can be voluntarily regulated, the neural bases of such faculty and its behavioural effects are yet insufficiently understood. In this study, we investigated how the instructions to execute a demanding cognitive task either "with maximum exertion" or "as relaxed as possible" affected performance and brain activity. The maximum exertion condition, compared to relaxed execution, was associated with speeded motor responses without an accuracy trade-off, and an amplification of both task-related activations in dorsal frontoparietal and cerebellar regions, and task-related deactivations in default mode network (DMN) areas. Furthermore, the visual cue to engage maximum effort triggered an anticipatory widespread increase of activity in attentional, sensory and executive regions, with its peak in the brain stem reticular activating system. Across individuals, this surge of activity in the brain stem, but also in medial wall cortical regions projecting to the adrenal medulla, positively correlated with increases in heart rate, suggesting that the intention to willfully modulate invested effort involves mechanisms related to catecholaminergic transmission and a suppression of DMN activity in favor of externally-directed attentional processes.

A cognitive-stimulation tool was created to regulate functional connectivity within the brain Default-Mode Network (DMN). Computerized exercises were designed based on the hypothesis that repeated task-dependent coactivation of multiple DMN regions would translate into regulation of resting-state network connectivity. Forty seniors (mean age: 65.90 years; SD: 8.53) were recruited and assigned either to an experimental group (n=21) who received one month of intensive cognitive stimulation, or to a control group (n=19) who maintained a regime of daily-life activities explicitly focused on social interactions. An MRI protocol and a battery of neuropsychological tests were administered at baseline and at the end of the study. Changes in the DMN (measured via functional connectivity of posterior-cingulate seeds), in brain volumes, and in cognitive performance were measured with mixed models assessing group-by-timepoint interactions. Moreover, regression models were run to test gray-matter correlates of the various stimulation tasks. Significant associations were found between task performance and gray-matter volume of multiple DMN core regions. Training-dependent up-regulation of functional connectivity was found in the posterior DMN component. This interaction was driven by a pattern of increased connectivity in the training group, while little or no up-regulation was seen in the control group. Minimal changes in brain volumes were found, but there was no change in cognitive performance. The training-dependent regulation of functional connectivity within the posterior DMN component suggests that this stimulation program might exert a beneficial impact in the prevention and treatment of early AD neurodegeneration, in which this neurofunctional pathway is progressively affected by the disease.

OBJECTIVE: To investigate the effect of the Apolipoprotein E (ApoE) e4 allele on the functional connectivity of the claustrum in mild cognitive impairment (MCI). BACKGROUND: The claustrum is reputed to play an important role in integrating multimodal sensory-motor information. It is believed to contribute to the integration of task-associated and resting-state networks and it is an important cholinergic hub. Although a number of studies have highlighted its involvement in prodromal and clinically-established Alzheimer9s disease (AD), the relationship between the claustrum and the most influential AD-associated genetic moderator (the ApoE e4 allele) is undetermined. DESIGN/METHODS: Twenty-two MCI patients (eleven ApoE e4e3 carriers, and eleven e3 homozygous) were included in this study. No inter-group difference emerged in demographic/cognitive variables or global measures of brain structure. Both MCI groups were of the amnestic type. All patients underwent resting-state fMRI scanning with a 1.5T Philips Achieva scanner. Preprocessing and analytical steps were carried out using SPM-8 and a set of well-established toolboxes. Individual maps of claustral connectivity were then computed regressing out motion, white-matter signal and cerebrospinal-fluid signal regressors. Two-sample t tests were run to determine the impact of the e4 allele on the connectivity maps. A significant p D D FWE <0.05 were considered significant. RESULTS: e4 carriers had increased connectivity between the left claustrum and left insula/orbitofrontal cortex, and between the right claustrum and the left precuneus. No decreased connectivity was found for e4 carriers. CONCLUSIONS: The evidence of increased functional connectivity with both the default mode network and its anticorrelated salience networks suggests additional circuital effort necessary for maintaining network-to-network integration. This suggests that MCI e4 carriers might be at more advanced stages of network disruption than e4 non-carriers. Disclosure: Dr. De Marco has nothing to disclose. Dr. Vallelunga has nothing to disclose. Dr. Duzzi has nothing to disclose. Dr. Meneghello has nothing to disclose. Dr. Venneri has received personal compensation for activities with Novartis.

Little is known about the neural bases of hypnotic suggestibility, a cognitive trait referring to the tendency to respond to hypnotic suggestions. In the present magnetic resonance imaging study, we performed regression analyses to assess hypnotic suggestibility-related differences in local gray matter volume, using voxel-based morphometry, and in waking resting state functional connectivity of 10 resting state networks, in 37 healthy women. Hypnotic suggestibility was positively correlated with gray matter volume in portions of the left superior and medial frontal gyri, roughly overlapping with the supplementary and pre-supplementary motor area, and negatively correlated with gray matter volume in the left superior temporal gyrus and insula. In the functional connectivity analysis, hypnotic suggestibility was positively correlated with functional connectivity between medial posterior areas, including bilateral posterior cingulate cortex and precuneus, and both the lateral visual network and the left fronto-parietal network; a positive correlation was also found with functional connectivity between the executive-control network and a right postcentral/parietal area. In contrast, hypnotic suggestibility was negatively correlated with functional connectivity between the right fronto-parietal network and the right lateral thalamus. These findings demonstrate for the first time a correlation between hypnotic suggestibility, the structural features of specific cortical regions, and the functional connectivity during the normal resting state of brain structures involved in imagery and self-monitoring activity.

The Mild Cognitive Impairment (MCI) stage of Alzheimer's disease (AD) features loss of both hippocampal volume and connectivity. Some studies found that, within this diagnostic stage, carrying a copy of the Apolipoprotein E (ApoE) ε 4 allele is associated with lower hippocampal volumes, while other studies reported no volumetric differences in association with this structure. No study has yet investigated ε 4 -dependent hippocampal connectivity in MCI. We recruited 12 MCI patients with a known ApoE ε 4 ε 3 genotype and a group of 12 ε 3 ε 3 MCI patients matched for age, years of education, total intracranial volume, total grey/white matter proportion, cognitive performance, and qualitative profile of cognitive impairment. Three dimensional structural T1-weigthed images and T2*-weighted resting-state scans were collected and preprocessed. Voxel-Based Morphometry was carried out on TW1 scans. Two seeds were drawn in the hippocampi, and individual whole-brain correlational maps of resting-state signal computed on functional scans. Two-sample t tests were used to compare structural and connectivity maps in the two groups. An uncorrected p value of 0.001 (structural analysis) or 0.005 (functional analysis) was used together with a cluster extent of 50 contiguous voxels. Peaks surviving Family-Wise Error correction were reported as significant. MCI patients with a ε 3 ε 3 genotype had larger grey matter volumes in the left superior temporal gyrus only. No white-matter difference was found. ε 4 carriers showed decreased connectivity between the left hippocampus and the left superior temporal gyrus, the posterior cingulate cortex and cuneus bilaterally and a left temporal white-matter cluster. Additionally, these patients showed increased connectivity between the right seed and a set of frontal areas. ε 4 carriers did not have smaller hippocampal volumes in our sample but had increased left-hippocampus disconnection from the core hub of the default mode network and from other neocortical clusters. This would reflect the left-to-right mediotemporal gradient of involvement observable along the timeline of AD progression, and suggests that ε 4 carriers are at a more advanced stage of neurodegeneration than matched ε 3 ε 3 individuals. We suggest that increased connectivity of the right hippocampus with frontal areas might reflect a consequent compensatory mechanism complimentary to the left-hemisphere decrease.

Mesial temporal lobe epilepsy (MTLE) can be associated with emotion recognition impairment that can be particularly severe in patients with early onset seizures (1-3). Whereas, there is growing evidence that memory and language can improve in seizure-free patients after anterior temporal lobectomy (ATL) (4), the effects of surgery on emotional processing are still unknown. We used functional magnetic resonance imaging (fMRI) to investigate short-term reorganization of networks engaged in facial emotion recognition in MTLE patients. Behavioral and fMRI data were collected from six patients before and after ATL. During the fMRI scan, patients were asked to make a gender decision on fearful and neutral faces. Behavioral data demonstrated that two patients with early onset right MTLE were impaired in fear recognition while fMRI results showed they lacked specific activations for fearful faces. Post-ATL behavioral data showed improved emotion recognition ability, while fMRI demonstrated the recruitment of a functional network for fearful face processing. Our results suggest that ATL elicited brain plasticity mechanisms allowing behavioral and fMRI improvement in emotion recognition.

The effect of transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) on psychopathological symptoms and resting state brain activity was assessed in a patient with obsessive-compulsive disorder (OCD). tDCS and rTMS had no effect on OC symptoms. tDCS, however, improved depression and anxiety. Functional magnetic resonance imaging at baseline showed an interhemispheric asymmetry with hyperactivation of the left and hypoactivation of the right anterior neural circuits. A reduction of interhemispheric imbalance was detected after tDCS but not after rTMS. tDCS seems to be more effective than rTMS in restoring interhemispheric imbalance and improving anxiety and depression in OCD.

Cholinesterase inhibitors (ChEIs) remain the first line of treatment in Alzheimer's disease (AD) and newer treatments have had no effect in clinical AD. It is possible that the limited effects of ChEIs might have been due to intervention being given too late in the course of the disease to interfere positively with the course of the disease. Preclinical evidence indicates that cholinesterase inhibition affects basic processes of AD pathogenesis and loss of cholinergic innervations contributes to an acceleration of AD pathological processes by jeopardizing the potential for neuroplasticity in the cerebral cortex. The object of this study therefore, was to assess using resting state fMRI if early treatment with rivastigmine improves functional connectivity within a limbico-cortical memory retrieval network when administered at the mild cognitive impairment stage. Patients with Mild Cognitive Impairment were treated for 12 weeks with rivastigmine in a within subject design with clinical, cognitive and resting state fMRI assessments before and after treatment. Changes in brain activation and in functional connectivity were the primary outcome measures. Increases in activity within areas of the Default Mode Network were observed following treatment and there also was regained functional connectivity between the hippocampus and the posterior cingulate, precuneus and right prefrontal cortex. All these regions of improved functional connectivity are essential components of a memory retrieval network. These improvements were paralleled by clinical and cognitive benefits. Treatment with a ChEI at an early preclinical MCI stage of AD triggered a neuroplastic effect and improved functional connectivity within crucial areas in the memory retrieval system. The findings suggest a different interpretation of a disease modifying effect of ChEI treatment indicating for the first time that early intervention can successfully trigger the residual potential for neuroplasticity within the AD brain with substantial effects on patients' cognition and quality of life.

OBJECTIVE: To assess using resting state fMRI if early treatment with rivastigmine improves functional connectivity within a limbico-cortical memory retrieval network when administered early in the course of the disease.