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.

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.

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.

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 / Lenguas y Psicoterapia: El Efecto de la Lengua Extranjera en la Extinción del Miedo

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.(AU)

Antecedentes: Usar un idioma extranjero puede influir la modulación de las emociones, pero no está claro si su uso podría influir diferentes procesos psicoterapéuticos. Este estudio explora el efecto de la lengua extranjera en la extinción del miedo. Método: Durante el condicionamiento, parte de los estímulos presentados se asociaron a amenaza, mientras los participantes realizaban una tarea de cuenta regresiva en un contexto de lengua nativa. En la fase de extinción, se realizó la misma tarea en su lengua nativa/extranjera, y se informó de que ya no habría amenaza. Se recogieron autoinformes de miedo, así como dilatación de pupila y actividad electrodérmica como medidas fisiológicas de excitación. Resultados: La extinción fue satisfactoria, como muestran una mayor dilatación pupilar y los autoinformes de miedo al comparar las condiciones de amenaza y neutral en la fase de condicionamiento, y no encontrar diferencias significativas durante la extinción. Aunque el grupo de lengua extranjera presentó una mayor excitación, la extinción del miedo ocurre independientemente del contexto lingüístico. Conclusiones: La extinción del miedo mediante instrucciones verbales es igualmente eficaz en contexto de lengua extranjera y nativa. Estos resultados invitan a seguir reuniendo pruebas sobre el papel de las lenguas extranjeras mediante paradigmas con aplicaciones clínicas.(AU)

Dynamic Effects of Immersive Bilingualism on Cortical and Subcortical Grey Matter Volumes.

Bilingualism has been shown to induce neuroplasticity in the brain, but conflicting evidence regarding its specific effects in grey matter continues to emerge, probably due to methodological differences between studies, as well as approaches that may miss the variability and dynamicity of bilingual experience. In our study, we devised a continuous score of bilingual experiences and we investigated their non-linear effects on regional GM volume in a sample of young healthy participants from an immersive and naturalistic bilingual environment. We focused our analyses on cortical and subcortical regions that had been previously proposed as part of the bilingual speech pipeline and language control network. Our results showed a non-linear relationship between bilingualism score and grey matter volume of the inferior frontal gyrus. We also found linear increases in volumes of putamen and cerebellum as a function of bilingualism score. These results go in line with predictions for immersive and naturalistic bilingual environments with increased intensity and diversity of language use and provide further evidence supporting the dynamicity of bilingualism's effects on brain structure.

Brain networks alterations in cocaine use and gambling disorders during emotion regulation.

Background: Cocaine use disorder (CUD) and gambling disorder (GD) share clinical features and neural alterations, including emotion regulation deficits and dysfunctional activation in related networks. However, they also exhibit differential aspects, such as the neuroadaptive effects of long-term drug consumption in CUD as compared to GD. Neuroimaging research aimed at disentangling their shared and specific alterations can contribute to improve understanding of both disorders. Methods: We compared CUD (N = 15), GD (N = 16) and healthy comparison (HC; N = 17) groups using a network-based approach for studying temporally coherent functional networks during functional magnetic resonance imaging (fMRI) of an emotion regulation task. We focused our analysis in limbic, ventral frontostriatal, dorsal attentional (DAN) and executive networks (FPN), given their involvement in emotion regulation and their alteration in CUD and GD. Correlations with measures of emotional experience and impulsivity (UPPS-P) were also performed. Results: The limbic network was significantly decreased during emotional processing both for CUD and GD individuals compared to the HC group. Furthermore, GD participants compared to HC showed an increased activation in the ventral frontostriatal network during emotion regulation. Finally, networks' activation patterns were modulated by impulsivity traits. Conclusions: Functional network analyses revealed both overlapping and unique effects of stimulant and gambling addictions on neural networks underpinning emotion regulation.

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.

The adhesio interthalamica as a neuroanatomical marker of structural differences in healthy adult population.

The adhesio interthalamica (AI) is a small midline brain structure that connects the left and right thalamus. According to in vivo data, between 2.3 and 22.3% of the general population lack the AI, and the question of whether this absence is more prevalent in males than in females is a matter of debate. Despite the existence of these demographic figures, it remains unclear how this distinctive feature affects healthy people, or what specific anatomic profile is related to the presence or absence of the AI. The aim of this study was to investigate whole-brain gray matter (GM) volumetric differences depending on the presence or absence of the AI. A total of 240 healthy adult volunteers completed one MRI scanning session. After the AI assessment, the data from 110 participants were included in the final sample, of which 12.9% of the participants (n = 31) presented complete AI absence vs. 32.9% of participants (n = 79) who presented complete AI presence. Then, whole-brain group comparison analysis revealed that the absent AI brain, compared to the present AI brain, was associated with lower GM volume in the premotor cortex, inferior frontal gyrus, and anterior temporal cortex. Interestingly, neuroscience research has linked emotional and cognitive control brain processing to the latter two regions. The importance of these findings lies in providing a neuroanatomical profile for the absent AI brain in healthy human adults.

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.

Foreign Language Processing Undermines Affect Labeling.

Identifying emotional states and explicitly putting them into words, known as affect labeling, reduces amygdala activation. Crucially, bilinguals do not only label emotions in their native language; they sometimes do it in their foreign language as well. However, one's foreign languages are less emotional and more cognitively demanding than one's native language. Because of these differences, it is unclear whether labeling emotions in a foreign language will also cause downregulation of affect. Here, 26 unbalanced bilinguals were scanned while labeling emotional faces either in their native or foreign languages. Results on affect labeling in a foreign language revealed that not only did it not reduce amygdala activation, but it also evoked higher activation than affect labeling in a native language. Overall, foreign language processing undermines affect labeling, and it suggests that the language in which people name their emotions has important consequences in how they experience them. Supplementary Information: The online version contains supplementary material available at 10.1007/s42761-021-00039-9.

Bilingualism's Effects on Resting-State Functional Connectivity in Mild Cognitive Impairment.

Background: Bilingualism is considered a cognitive reserve (CR) factor, due to the delay in the onset of dementia in bilinguals compared with monolinguals. Two neural mechanisms have been suggested to underlie CR: neural reserve and neural compensation. However, it is still unclear how bilingualism contributes to these mechanisms. Methods: In this study, we used cognitive tests, functional connectivity (FC), regional homogeneity, and fractional amplitude of low-frequency fluctuations (fALFF) measures to study resting-state brain patterns in a sample of bilingual and monolingual subjects with mild cognitive impairment. Results: We found no significant differences between the groups in age, sex, education, or cognitive level, but bilinguals showed higher FC than monolinguals between the posterior part of the superior temporal gyrus and the precuneus, positively correlated with Mini-Mental State Examination scores, and higher fALFF in the thalamus bilaterally. Conclusions: Our results suggest that bilingualism may act as a CR factor that protects against dementia through neural compensation.

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.

Correction to: Auditory and frontal anatomic correlates of pitch discrimination in musicians, non­musicians, and children without musical training.

In the original version of the article, the abstract section was missed to be added, and the abstract should read as below.

Auditory and frontal anatomic correlates of pitch discrimination in musicians, non-musicians, and children without musical training.

Individual differences in pitch discrimination have been associated with the volume of both the bilateral Heschl's gyrus and the right inferior frontal gyrus (IFG). However, most of these studies used samples composed of individuals with different amounts of musical training. Here, we investigated the relationship between pitch discrimination and individual differences in the gray matter (GM) volume of these brain structures in 32 adult musicians, 28 adult non-musicians, and 32 children without musical training. The results showed that (i) the individuals without musical training (whether children or adults) who were better at pitch discrimination had greater volume of auditory regions, whereas (ii) musicians with better pitch discrimination had greater volume of the IFG. These results suggest that the relationship between pitch discrimination and the volume of auditory regions is innately established early in life, and that musical training modulates the volume of the IFG, probably improving audio-motor connectivity. This is the first study to detect a relationship between pitch discrimination ability and GM volume before beginning any musical training in children and adults.

Opening or closing eyes at rest modulates the functional connectivity of V1 with default and salience networks.

Current evidence suggests that volitional opening or closing of the eyes modulates brain activity and connectivity. However, how the eye state influences the functional connectivity of the primary visual cortex has been poorly investigated. Using the same scanner, fMRI data from two groups of participants similar in age, sex and educational level were acquired. One group (n = 105) performed a resting state with eyes closed, and the other group (n = 63) performed a resting state with eyes open. Seed-based voxel-wise functional connectivity whole-brain analyses were performed to study differences in the connectivity of the primary visual cortex. This region showed higher connectivity with the default mode and sensorimotor networks in the eyes closed group, but higher connectivity with the salience network in the eyes open group. All these findings were replicated using an open source shared dataset. These results suggest that opening or closing the eyes may set brain functional connectivity in an interoceptive or exteroceptive state.

Individual Differences in Hippocampal Volume as a Function of BMI and Reward Sensitivity.

Sensitivity to reward is a personality trait that predisposes a person to several addictive behaviors, including the presence of different risky behaviors that facilitates uncontrolled eating. However, the multifactorial nature of obesity blurs a direct relationship between the two factors. Here, we studied the brain anatomic correlates of the interaction between reward sensitivity and body mass index (BMI) to investigate whether the coexistence of high BMI and high reward sensitivity structurally alters brain areas specifically involved in the regulation of eating behavior. To achieve this aim, we acquired T1-weighted images and measured reward sensitivity using the Sensitivity to Punishment and Sensitivity to Reward Questionnaire (SPSRQ) and BMI in a sample of 206 adults. Results showed that reward sensitivity and BMI were not significantly correlated. However, neuroimaging results confirmed a relationship between BMI and reduced volume in the medial and lateral orbitofrontal cortex, and between reward sensitivity and lower striatum volume. Importantly, the interaction between the two factors was significantly related to the right anterior hippocampus volume, showing that stronger reward sensitivity plus a higher BMI were associated with reduced hippocampal volume. The hippocampus is a brain structure involved in the higher-order regulation of feeding behavior. Thus, a dysfunctional hippocampus may contribute to maintaining a vicious cycle that predisposes people to obesity.

Distance disintegration delineates the brain connectivity failure of Alzheimer's disease.

Alzheimer's disease (AD) is associated with brain network dysfunction. Network-based investigations of brain connectivity have mainly focused on alterations in the strength of connectivity; however, the network breakdown in AD spectrum is a complex scenario in which multiple pathways of connectivity are affected. To integrate connectivity changes that occur under AD-related conditions, here we developed a novel metric that computes the connectivity distance between cortical regions at the voxel level (or nodes). We studied 114 individuals with mild cognitive impairment, 24 with AD, and 27 healthy controls. Results showed that areas of the default mode network, salience network, and frontoparietal network display a remarkable network separation, or greater connectivity distances, from the rest of the brain. Furthermore, this greater connectivity distance was associated with lower global cognition. Overall, the investigation of AD-related changes in paths and distances of connectivity provides a novel framework for characterizing subjects with cognitive impairment; a framework that integrates the overall network topology changes of the brain and avoids biases toward unreferenced connectivity effects.

A cross-sectional and longitudinal study on the protective effect of bilingualism against dementia using brain atrophy and cognitive measures.

BACKGROUND: Evidence from previous studies suggests that bilingualism contributes to cognitive reserve because bilinguals manifest the first symptoms of Alzheimer's disease (AD) up to 5 years later than monolinguals. Other cross-sectional studies demonstrate that bilinguals show greater amounts of brain atrophy and hypometabolism than monolinguals, despite sharing the same diagnosis and suffering from the same symptoms. However, these studies may be biased by possible pre-existing between-group differences. METHODS: In this study, we used global parenchymal measures of atrophy and cognitive tests to investigate the protective effect of bilingualism against dementia cross-sectionally and prospectively, using a sample of bilinguals and monolinguals in the same clinical stage and matched on sociodemographic variables. RESULTS: Our results suggest that the two groups did not differ in their cognitive status at baseline, but bilinguals had less parenchymal volume than monolinguals, especially in areas related to brain atrophy in dementia. In addition, a longitudinal prospective analysis revealed that monolinguals lost more parenchyma and had more cognitive decline than bilinguals in a mean follow-up period of 7 months. CONCLUSION: These results provide the first prospective evidence that bilingualism may act as a neuroprotective factor against dementia and could be considered a factor in cognitive reserve.