The manifestation of individual differences in sensitivity to punishment during resting state is modulated by eye state.

Structural and functional neuroimaging studies have shown that brain areas associated with fear and anxiety (defensive system areas) are modulated by individual differences in sensitivity to punishment (SP). However, little is known about how SP is related to brain functional connectivity and the factors that modulate this relationship. In this study, we investigated whether a simple methodological manipulation, such as performing a resting state with eyes open or eyes closed, can modulate the manifestation of individual differences in SP. To this end, we performed an exploratory fMRI resting state study in which a group of participants (n = 88) performed a resting state with eyes closed and another group (n = 56) performed a resting state with eyes open. All participants completed the Sensitivity to Punishment and Sensitivity to Reward Questionnaire. Seed-based functional connectivity analyses were performed in the amygdala, hippocampus, and periaqueductal gray (PAG). Our results showed that the relationship between SP and left amygdala-precuneus and left hippocampus-precuneus functional connectivity was modulated by eye state. Moreover, in the eyes open group, SP was negatively related to the functional connectivity between the PAG and amygdala and between the PAG and left hippocampus, and it was positively related to the functional connectivity between the amygdala and hippocampus. Together, our results may suggest underlying differences in the connectivity between anxiety-related areas based on eye state, which in turn would affect the manifestation of individual differences in SP.

Sustained and transient gray matter volume changes after n-back training: A VBM study.

Working memory training causes functional adaptations in the brain, which include changes in activation and functional connectivity that remain stable over time. Few studies have investigated gray matter (GM) changes after working memory training, and they have produced heterogeneous results without clarifying the stable effects of training. The present study was designed to test for sustained and transient anatomic changes after only 200 min of working memory training. The voxel-based morphometry technique was used in order to investigate the GM changes produced by a brief single n-back training, immediately and 5 weeks after finishing it. The sample was composed by 59 human participants who underwent MRI scanning and were assigned to either a training group or a passive control group. Results showed sustained GM volume enlargement in the right superior parietal cortex and a transient GM decrease in the right putamen. The brain adaptation in the right superior parietal cortex was stronger in individuals who showed greater improvements in performance. The results provide further evidence that a brief working memory training is able to produce brain plasticity in structures related to the trained task.

Distance disintegration characterizes node-level topological dysfunctions in cocaine addiction.

Previous investigations have used global graph theory measures in order to disentangle the complexity of the neural reorganizations occurring in cocaine use disorder (CUD). However, how these global topological alterations map into individual brain network areas remains unknown. In this study, we used resting state functional magnetic resonance imaging (fMRI) data to investigate node-level topological dysfunctions in CUD. The sample was composed of 32 individuals with CUD and 32 healthy controls, matched in age, years of education and intellectual functioning. Graph theory measures of optimal connectivity distance, node strength, nodal efficiency and clustering coefficient were estimated in each participant using voxel-wise functional connectivity connectomes. CUD individuals as compared with healthy controls showed higher optimal connectivity distances in ventral striatum, insula, cerebellum, temporal cortex, lateral orbitofrontal cortex, middle frontal cortex and left hippocampus. Furthermore, clinical measures quantifying severity of dependence were positively related with optimal connectivity distances in the right rolandic operculum and the right lateral orbitofrontal cortex, whereas length of abstinence was negatively associated with optimal connectivity distances in the right temporal pole and the left insula. Our results reveal a topological distancing of cognitive and affective related areas in addiction, suggesting an overall reduction in the communication capacity of these regions.

Motivational factors modulate left frontoparietal network during cognitive control in cocaine addiction.

Cocaine addiction is characterized by alterations in motivational and cognitive processes involved in goal-directed behavior. Recent studies have shown that addictive behaviors can be attributed to alterations in the activity of large functional networks. The aim of this study was to investigate how cocaine addiction affected the left frontoparietal network during goal-directed behavior in a stop-signal task (SST) with reward contingencies by correct task performance. Twenty-eight healthy controls (HC) and 30 abstinent cocaine-dependent patients (ACD) performed SST with monetary reward contingencies while undergoing a functional magnetic resonance imaging scan. The results showed that the left frontoparietal network (FPN) displayed an effect of cocaine addiction depending on reward contingencies rather than inhibition accuracy; and, second, we observed a negative correlation between dependence severity and the modulation of the left FPN network by the monetary reward in ACD. These findings highlight the role of the left FPN in the motivational effects of cocaine dependence.

Brain circuit-gene expression relationships and neuroplasticity of multisensory cortices in blind children.

Sensory deprivation reorganizes neurocircuits in the human brain. The biological basis of such neuroplastic adaptations remains elusive. In this study, we applied two complementary graph theory-based functional connectivity analyses, one to evaluate whole-brain functional connectivity relationships and the second to specifically delineate distributed network connectivity profiles downstream of primary sensory cortices, to investigate neural reorganization in blind children compared with sighted controls. We also examined the relationship between connectivity changes and neuroplasticity-related gene expression profiles in the cerebral cortex. We observed that multisensory integration areas exhibited enhanced functional connectivity in blind children and that this reorganization was spatially associated with the transcription levels of specific members of the cAMP Response Element Binding protein gene family. Using systems-level analyses, this study advances our understanding of human neuroplasticity and its genetic underpinnings following sensory deprivation.

Reward network connectivity "at rest" is associated with reward sensitivity in healthy adults: A resting-state fMRI study.

The behavioral approach system (BAS), based on reinforcement sensitivity theory (RST), is a neurobehavioral system responsible for detecting and promoting motivated behaviors towards appetitive stimuli. Anatomically, the frontostriatal system has been proposed as the core of the BAS, mainly the ventral tegmental area and the ventral striatum and their dopaminergic connections with medial prefrontal structures. The RST also proposes the personality trait of reward sensitivity as a measurable construct of stable individual differences in BAS activity. However, the relationship between this trait and brain connectivity "at rest" has been poorly studied, mainly because previous investigations have focused on studying brain activity under reward-related contingency paradigms. Here, we analyzed the influence of reward sensitivity on the resting-state functional connectivity (rs-FC) between BAS-related areas by correlating the BOLD time series with the scores on the Sensitivity to Reward (SR) scale in a sample of 89 healthy young adults. Rs-FC between regions of interest were all significant. Results also revealed a positive association between SR scores and the rs-FC between the VTA and the ventromedial prefrontal cortex, and between the latter structure and the anterior cingulate cortex. These results suggest that reward sensitivity could be associated with different resting-state activity in the mesocortical pathway.

Demotivating outcome of asymmetrical Nucleus Accumbens disconnection for cocaine related disorder: a translational point of view. / Desmotivadora evolución de la desconexión asimétrica del Núcleo Accumbens en el trastorno por consumo de cocaína: un punto de vista traslacional.

Letter to the editor.

Carta al editor.

Complexity analysis of cortical surface detects changes in future Alzheimer's disease converters.

Alzheimer's disease (AD) is a neurological disorder that creates neurodegenerative changes at several structural and functional levels in human brain tissue. The fractal dimension (FD) is a quantitative parameter that characterizes the morphometric variability of the human brain. In this study, we investigate spherical harmonic-based FD (SHFD), thickness, and local gyrification index (LGI) to assess whether they identify cortical surface abnormalities toward the conversion to AD. We study 33 AD patients, 122 mild cognitive impairment (MCI) patients (50 MCI converters and 29 MCI nonconverters), and 32 healthy controls (HC). SHFD, thickness, and LGI methodology allowed us to perform not only global level but also local level assessments in each cortical surface vertex. First, we found that global SHFD decreased in AD and future MCI converters compared to HC, and in MCI converters compared to MCI nonconverters. Second, we found that local white matter SHFD was reduced in AD compared to HC and MCI mainly in medial temporal lobe. Third, local white-matter SHFD was significantly reduced in MCI converters compared to MCI nonconverters in distributed areas, including the medial frontal lobe. Thickness and LGI metrics presented a reduction in AD compared to HC. Thickness was significantly reduced in MCI converters compared to healthy controls in entorhinal cortex and lateral temporal. In summary, SHFD was the only surface measure showing differences between MCI individuals that will convert or remain stable in the next 4 years. We suggest that SHFD may be an optimal complement to thickness loss analysis in monitoring longitudinal changes in preclinical and clinical stages of AD. Hum Brain Mapp 38:5905-5918, 2017. © 2017 Wiley Periodicals, Inc.

Reduced activity in functional networks during reward processing is modulated by abstinence in cocaine addicts.

Cocaine addiction is characterized by alterations in motivational and cognitive processes. Recent studies have shown that some alterations present in cocaine users may be related to the activity of large functional networks. The aim of this study was to investigate how these functional networks are modulated by non-drug rewarding stimuli in cocaine-dependent individuals. Twenty abstinent cocaine-dependent and 21 healthy matched male controls viewed erotic and neutral pictures while undergoing a functional magnetic resonance imaging scan. Group independent component analysis was then performed in order to investigate how functional networks were modulated by reward in cocaine addicts. The results showed that cocaine addicts, compared with healthy controls, displayed diminished modulation of the left frontoparietal network in response to erotic pictures, specifically when they were unpredicted. Additionally, a positive correlation between the length of cocaine abstinence and the modulation of the left frontoparietal network by unpredicted erotic images was found. In agreement with current addiction models, our results suggest that cocaine addiction contributes to reduce sensitivity to rewarding stimuli and that abstinence may mitigate this effect.

Characterizing individual differences in reward sensitivity from the brain networks involved in response inhibition.

A "disinhibited" cognitive profile has been proposed for individuals with high reward sensitivity, characterized by increased engagement in goal-directed responses and reduced processing of negative or unexpected cues, which impairs adequate behavioral regulation after feedback in these individuals. This pattern is manifested through deficits in inhibitory control and/or increases in RT variability. In the present work, we aimed to test whether this profile is associated with the activity of functional networks during a stop-signal task using independent component analysis (ICA). Sixty-one participants underwent fMRI while performing a stop-signal task, during which a manual response had to be inhibited. ICA was used to mainly replicate the functional networks involved in the task (Zhang and Li, 2012): two motor networks involved in the go response, the left and right fronto-parietal networks for stopping, a midline error-processing network, and the default-mode network (DMN), which was further subdivided into its anterior and posterior parts. Reward sensitivity was mainly associated with greater activity of motor networks, reduced activity in the midline network during correct stop trials and, behaviorally, increased RT variability. All these variables explained 36% of variance of the SR scores. This pattern of associations suggests that reward sensitivity involves greater motor engagement in the dominant response, more distractibility and reduced processing of salient or unexpected events, which may lead to disinhibited behavior.

How bilingualism shapes the functional architecture of the brain: A study on executive control in early bilinguals and monolinguals.

The existence of a behavioral advantage of bilinguals over monolinguals during executive tasks is controversial. A new approach to this issue is to investigate the effect of bilingualism on neural control when performing these tasks as a window to understand when behavioral differences are produced. Here, we tested if early bilinguals use more language-related networks than monolinguals while performing a go/no-go task that includes infrequent no-go and go trials. The RTs and accuracy in both groups did not differ. An independent component analyses (ICA) revealed, however, that bilinguals used the left fronto-parietal network and the salience network more than monolinguals while processing go infrequent cues and no-go cues, respectively. It was noteworthy that the modulation of these networks had opposite correlates with performance in bilinguals and monolinguals, which suggests that between-group differences were more qualitative than quantitative. Our results suggest that bilinguals may differently develop the involvement of the executive control networks that comprise the left inferior frontal gyrus during cognitive control tasks than monolinguals.

Reward anticipation enhances brain activation during response inhibition.

The chance to achieve a reward starts up the required neurobehavioral mechanisms to adapt our thoughts and actions in order to accomplish our objective. However, reward does not equally reinforce everybody but depends on interindividual motivational dispositions. Thus, immediate reward contingencies can modulate the cognitive process required for goal achievement, while individual differences in personality can affect this modulation. We aimed to test the interaction between inhibition-related brain response and motivational processing in a stop signal task by reward anticipation and whether individual differences in sensitivity to reward (SR) modulate such interaction. We analyzed the cognitive-motivational interaction between the brain pattern activation of the regions involved in correct and incorrect response inhibition and the association between such brain activations and SR scores. We also analyzed the behavioral effects of reward on both reaction times for the "go" trials before and after correct and incorrect inhibition in order to test error prediction performance and postinhibition adjustment. Our results show enhanced activation during response inhibition under reward contingencies in frontal, parietal, and subcortical areas. Moreover, activation of the right insula and the left putamen positively correlates with the SR scores. Finally, the possibility of reward outcome affects not only response inhibition performance (e.g., reducing stop signal reaction time), but also error prediction performance and postinhibition adjustment. Therefore, reward contingencies improve behavioral performance and enhance brain activation during response inhibition, and SR is related to brain activation. Our results suggest the conditions and factors that subserve cognitive control strategies in cognitive motivational interactions during response inhibition.

Abstinence duration modulates striatal functioning during monetary reward processing in cocaine patients.

Pre-clinical and clinical studies in cocaine addiction highlight alterations in the striatal dopaminergic reward system that subserve maintenance of cocaine use. Using an instrumental conditioning paradigm with monetary reinforcement, we studied striatal functional alterations in long-term abstinent cocaine-dependent patients and striatal functioning as a function of abstinence and treatment duration. Eighteen patients and 20 controls underwent functional magnetic resonance imaging during a Monetary Incentive Delay task. Region of interest analyses based on masks of the dorsal and ventral striatum were conducted to test between-group differences and the functional effects in the cocaine group of time (in months) with no more than two lapses from the first time patients visited the clinical service to seek treatment at the scanning time (duration of treatment), and the functional effects of the number of months with no lapses or relapses at the scanning session time (length of abstinence). We applied a voxel-wise and a cluster-wise FWE-corrected level (pFWE) at a threshold of P < 0.05. The patient group showed lower activation in the right caudate during reward anticipation than the control group. The regression analyses in the patients group revealed a positive correlation between duration of treatment and brain activity in the left caudate during reward anticipation. Likewise, length of abstinence negatively correlated with brain activity in the bilateral nucleus accumbens during monetary outcome processing. In conclusion, caudate and nucleus accumbens show a different brain response pattern to non-drug rewards during cocaine addiction, which can be modulated by treatment success.

Depression and Agitation Factors Are Related to Regional Brain Atrophy and Faster Longitudinal Cognitive Decline in Mild Cognitive Impairment.

BACKGROUND: Neuropsychiatric symptoms (NPS) are a common aspect of Alzheimer's disease (AD). Multiple studies have investigated its brain correlates, but it still remains unclear how they relate with brain atrophy in mild cognitive impairment (MCI). OBJECTIVE: Our objective was to investigate brain volume in MCI patients as a function of NPS. METHODS: We measured grey matter volume, neuropsychological status and NPS (Neuropsychiatric Inventory, NPI), in a sample of 81 MCI patients (43 females). Participants were divided in groups depending on presence (NPS+) or absence (NPS-) of NPS and on type of NPS. RESULTS: We found lower volume of left temporal pole in patients with depression compared to NPS- (p = 0.012), and in patients with agitation compared to NPS- in the right middle occipital gyrus (p = 0.003). We also found a significant correlation between volume of left temporal pole and MMSE (r (78) â€Š= 0.232, p = 0.019). Finally, NPS+ presented lower cross-sectional cognitive level than NPS- (t (79) â€Š= 1.79, p = 0.038), and faster cognitive decline (t (48) â€Š= -1.74, p = 0.044). CONCLUSIONS: Our results support the colocalization of structural damage as a possible mechanism underlying the relationship between MCI and depression and provide novel evidence regarding agitation. Moreover, our longitudinal evidence highlights the relevance of an adequate identification of NPS in MCI patients to identify those at risk of faster cognitive decline.

Reward sensitivity modulates connectivity among reward brain areas during processing of anticipatory reward cues.

Reward sensitivity, or the tendency to engage in motivated approach behavior in the presence of rewarding stimuli, may be a contributory factor for vulnerability to disinhibitory behaviors. Although evidence exists for a reward sensitivity-related increased response in reward brain areas (i.e. nucleus accumbens or midbrain) during the processing of reward cues, it is unknown how this trait modulates brain connectivity, specifically the crucial coupling between the nucleus accumbens, the midbrain, and other reward-related brain areas, including the medial orbitofrontal cortex and the amygdala. Here, we analysed the relationship between effective connectivity and personality in response to anticipatory reward cues. Forty-four males performed an adaptation of the Monetary Incentive Delay Task and completed the Sensitivity to Reward scale. The results showed the modulation of reward sensitivity on both activity and functional connectivity (psychophysiological interaction) during the processing of incentive cues. Sensitivity to reward scores related to stronger activation in the nucleus accumbens and midbrain during the processing of reward cues. Psychophysiological interaction analyses revealed that midbrain-medial orbitofrontal cortex connectivity was negatively correlated with sensitivity to reward scores for high as compared with low incentive cues. Also, nucleus accumbens-amygdala connectivity correlated negatively with sensitivity to reward scores during reward anticipation. Our results suggest that high reward sensitivity-related activation in reward brain areas may result from associated modulatory effects of other brain regions within the reward circuitry.

Reading salt activates gustatory brain regions: fMRI evidence for semantic grounding in a novel sensory modality.

Because many words are typically used in the context of their referent objects and actions, distributed cortical circuits for these words may bind information about their form with perceptual and motor aspects of their meaning. Previous work has demonstrated such semantic grounding for sensorimotor, visual, auditory, and olfactory knowledge linked to words, which is manifest in activation of the corresponding areas of the cortex. Here, we explore the brain basis of gustatory semantic links of words whose meaning is primarily related to taste. In a blocked functional magnetic resonance imaging design, Spanish taste words and control words matched for a range of factors (including valence, arousal, image-ability, frequency of use, number of letters and syllables) were presented to 59 right-handed participants in a passive reading task. Whereas all the words activated the left inferior frontal (BA44/45) and the posterior middle and superior temporal gyri (BA21/22), taste-related words produced a significantly stronger activation in these same areas and also in the anterior insula, frontal operculum, lateral orbitofrontal gyrus, and thalamus among others. As these areas comprise primary and secondary gustatory cortices, we conclude that the meaning of taste words is grounded in distributed cortical circuits reaching into areas that process taste sensations.

Structural But Not Functional Connectivity Differences within Default Mode Network Indicate Conversion to Dementia.

BACKGROUND: Malfunctioning of the default mode network (DMN) has been consistently related to mild cognitive impairment (MCI) and Alzheimer's disease (AD). However, evidence on differences in this network between MCI converters (MCI-c) and non-converters (MCI-nc), which could mark progression to AD, is still inconsistent. OBJECTIVE: To multimodally investigate the DMN in the AD continuum. METHODS: We measured gray matter (GM) volume, white matter (WM) integrity, and functional connectivity (FC) at rest in healthy elderly controls, MCI-c, MCI-nc, and AD patients, matched on sociodemographic variables. RESULTS: Significant differences between AD patients and controls were found in the structure of most of the regions of the DMN. MCI-c only differed from MCI-nc in GM volume of the left parahippocampus and bilateral hippocampi and middle frontal gyri, as well as in WM integrity of the parahippocampal cingulum connecting the left hippocampus and precuneus. We found significant correlations between integrity in some of those regions and global neuropsychological status, as well as an excellent discrimination ability between converters and non-converters for the sum of GM volume of left parahippocampus, bilateral hippocampi, and middle frontal gyri, and WM integrity of left parahippocampal cingulum. However, we found no significant differences in FC. CONCLUSION: These results further support the relationship between abnormalities in the DMN and AD, and suggest that structural measures could be more accurate than resting-state estimates as markers of conversion from MCI to AD.

Underlying differences in resting-state activity metrics related to sensitivity to punishment.

Reinforcement sensitivity theory (RST) of personality establishes the punishment sensitivity trait as a source of variation in defensive avoidance/approach behaviors. These individual differences reflect dissimilar sensitivity and reactivity of the fight-flight-freeze and behavioral inhibition systems (FFFS/BIS). The sensitivity to punishment (SP) scale has been widely used in personality research aimed at studying the activity of these systems. Structural and functional neuroimaging studies have confirmed the core biological correlates of FFFS/BIS in humans. Nonetheless, some brain functional features derived from resting-state blood-oxygen level-dependent (BOLD) activity and its association with the punishment sensitivity dimension remain unclear. This relationship would shed light on stable neural activity patterns linked to anxiety-like behaviors and anxiety predisposition. In this study, we analyzed functional activity metrics "at rest" [e.g., regional homogeneity (ReHo) and fractional amplitude of low-frequency fluctuation (fALFF)] and their relationship with SP in key FFFS/BIS regions (e.g., amygdala, hippocampus, and periaqueductal gray) in a sample of 127 healthy adults. Our results revealed a significant negative correlation between the fALFF within all these regions and the scores on SP. Our findings suggest aberrant neural activity (lower fALFF) within the brain's defense system in participants with high trait anxiety, which in turn could reflect lower FFFS/BIS activation thresholds. These neurally-located differences could lead to pathological fear/anxiety behaviors arising from the FFFS and BIS.

Languages and Psychotherapy: The Effect of Foreign Language on Fear Extinction.

BACKGROUND: Using a foreign language can influence emotion modulation, but whether different psychotherapy processes would be affected by a foreign language is still unclear. The current study explored the foreign language effect on the extinction of fear. METHOD: During the conditioning phase, part of the neutral stimuli presented to the participants were associated with a threat, while they performed a countdown task in their native language. In the extinction phase, participants performed the same task either in their native/foreign language and were informed that the threat would no longer appear. We collected self-reports of fear, and pupil dilation and electrodermal activity as physiological measures of arousal. RESULTS: Extinction was successful, indicated by greater self-reported fear and pupil dilation during the threat condition compared to neutral in the conditioning phase, but no significant differences during extinction. Although the foreign language group presented higher arousal, fear extinction occurred regardless of the linguistic context. CONCLUSIONS: Fear extinction via verbal instructions is equally effective in a foreign and a native language context. These results indicate that evidence should be continue to be gathered on the role of foreign languages using basic paradigms with clinical applications.

Two different brain networks underlying picture naming with familiar pre-existing native words and new vocabulary.

The present research used fMRI to longitudinally investigate the impact of learning new vocabulary on the activation pattern of the language control network by measuring BOLD signal changes during picture naming tasks with familiar pre-existing native words (old words) and new vocabulary. Nineteen healthy participants successfully learned new synonyms for already known Spanish words, and they performed a picture naming task using the old words and the new words immediately after learning and two weeks after learning. The results showed that naming with old words, compared to naming with newly learned words, produced activations in a cortical network involving frontal and parietal regions, whereas the opposite contrast showed activation in a broader cortical/subcortical network, including the SMA/ACC, the hippocampus, and the midbrain. These two networks are maintained two weeks after learning. These results suggest that the language control network can be separated into two functional circuits for diverse cognitive purposes.