Medial Frontal Pole Research Articles

Diminished reinforcement sensitivity in adolescence is associated with enhanced response switching and reduced coding of choice probability in the medial frontal pole

Precisely charting the maturation of core neurocognitive functions such as reinforcement learning (RL) and flexible adaptation to changing action-outcome contingencies is key for developmental neuroscience and adjacent fields like developmental psychiatry. However, research in this area is both sparse and conflicted, especially regarding potentially asymmetric development of learning for different motives (obtain wins vs avoid losses) and learning from valenced feedback (positive vs negative). In the current study, we investigated the development of RL from adolescence to adulthood, using a probabilistic reversal learning task modified to experimentally separate motivational context and feedback valence, in a sample of 95 healthy participants between 12 and 45. We show that adolescence is characterized by enhanced novelty seeking and response shifting especially after negative feedback, which leads to poorer returns when reward contingencies are stable. Computationally, this is accounted for by reduced impact of positive feedback on behavior. We also show, using fMRI, that activity of the medial frontopolar cortex reflecting choice probability is attenuated in adolescence. We argue that this can be interpreted as reflecting diminished confidence in upcoming choices. Interestingly, we find no age-related differences between learning in win and loss contexts.

Transcranial photobiomodulation changes topology, synchronizability, and complexity of resting state brain networks

Objective. Transcranial photobiomodulation (tPBM) is a recently proposed non-invasive brain stimulation approach with various effects on the nervous system from the cells to the whole brain networks. Specially in the neural network level, tPBM can alter the topology and synchronizability of functional brain networks. However, the functional properties of the neural networks after tPBM are still poorly clarified. Approach. Here, we employed electroencephalography and different methods (conventional and spectral) in the graph theory analysis to track the significant effects of tPBM on the resting state brain networks. The non-parametric statistical analysis showed that just one short-term tPBM session over right medial frontal pole can significantly change both topological (i.e. clustering coefficient, global efficiency, local efficiency, eigenvector centrality) and dynamical (i.e. energy, largest eigenvalue, and entropy) features of resting state brain networks. Main results. The topological results revealed that tPBM can reduce local processing, centrality, and laterality. Furthermore, the increased centrality of central electrode was observed. Significance. These results suggested that tPBM can alter topology of resting state brain network to facilitate the neural information processing. On the other hand, the dynamical results showed that tPBM reduced stability of synchronizability and increased complexity in the resting state brain networks. These effects can be considered in association with the increased complexity of connectivity patterns among brain regions and the enhanced information propagation in the resting state brain networks. Overall, both topological and dynamical features of brain networks suggest that although tPBM decreases local processing (especially in the right hemisphere) and disrupts synchronizability of network, but it can increase the level of information transferring and processing in the brain network.

Anterior prefrontal brain activity during emotion control predicts resilience to post-traumatic stress symptoms.

Regulating social emotional actions is essential for coping with life stressors and is associated with control by the anterior prefrontal cortex (aPFC) over the amygdala. However, it remains unclear to what extent prefrontal emotion regulation capacities contribute to resilience against developing post-traumatic stress disorder (PTSD) symptoms. Here, 185 police recruits who experienced their core trauma in the line of duty participated ina prospective longitudinal study. Pre-and post-trauma, they performed a well-established functionalMRI approach-avoidance task, mapping impulsive and controlled emotional actions. Higher baseline aPFC, dorsal and medial frontal pole activity was related to lower PTSD-symptoms after trauma exposure.aPFC activity predicted symptom development over and above self-reported and behavioral measures. Trauma-exposure, but not trauma-symptoms, predicted amygdala activation at follow-up. These findings suggest that prefrontal emotion regulation activity predicts increased resilience against developing post-traumatic stress symptoms, and may provide fruitful starting points for prediction and intervention studies.

Emerging beta‐amyloid pathology is associated with tau, synaptic, neurodegeneration and gray matter volume differences

AbstractBackgroundNew clinical trials, like the A3, are targeting participants with emerging amyloid pathology (between 20‐40 centiloids (CL). The aim of this study is to describe if there are detectable differences in tau, synaptic, inflammatory, neurodegeneration CSF markers and brain structure in participants with emerging amyloid pathology.MethodCSF Aß42, Aß40, t‐tau, p‐tau, neurogranin, GFAP, IL‐6, YKL‐40, sTREM2, NfL, S100B and α‐synuclein were measured with Elecsys® CSF assays and the Roche NeuroToolKit robust prototype assays in 303 cognitively unimpaired participants of the ALFA+ cohort. Participants also underwent APOE genotyping, structural MRI, as well as [18F]flutemetamol PET. Emerging amyloid pathology was defined in two different ways for checking results consistency: (1) Participants with less than 40 CL and a positive Aß42/40 ratio to be compared with those having less than 20 CL and a negative ratio (amyloid‐negative) and those with more than 40 CL and a positive ratio (amyloid‐positive). (2) Participants having between 20‐40 CL to be compared with those having less than 20 CL (amyloid‐negative) and more than 40 (amyloid‐positive). All CSF biomarker levels were compared between the emerging amyloid and its corresponding amyloid‐negative and ‐positive groups. SPM12 was used to seek for differences in gray matter volumes (GMv) among groups, after accounting for age, sex, APOE, education.Result89 and 16 participants fulfilled emergent amyloid criteria 1 and 2 respectively (demographics Table 1). Compared to the amyloid‐negative group, significantly increased levels of CSF p‐tau, t‐tau, neurogranin, and NfL could already be observed in the emerging amyloid group (both definitions, Figure 1a), whereas the remaining biomarkers only demonstrated increased abnormality in the amyloid‐positive group. Subjects with emerging amyloid pathology compared with the amyloid‐negative ones had greater GMv in the angular, supramarginal, fusiform, anterior temporal and medial frontal pole (Figure 1b). The association of the GMv differences and its interactions with the different biomarkers will also be presented.ConclusionThese results provide evidence that multiple biological pathways, such as tau, synaptic and neurodegenerative, are already altered in participants with emergent amyloid pathology, which also have greater gray matter volumes. Therefore, intervening very early in the Alzheimer’s continuum may be a priority.

Subgenual anterior cingulate cortex controls sadness-induced modulations of cognitive and emotional network hubs

The regulation of cognitive and emotional processes is critical for proper executive functions and social behavior, but its specific mechanisms remain unknown. Here, we addressed this issue by studying with functional magnetic resonance imaging the changes in network topology that underlie competitive interactions between emotional and cognitive networks in healthy participants. Our behavioral paradigm contrasted periods with high emotional and cognitive demands by including a sadness provocation task followed by a spatial working memory task. The sharp contrast between successive tasks was designed to enhance the separability of emotional and cognitive networks and reveal areas that regulate the flow of information between them (hubs). By applying graph analysis methods on functional connectivity between 20 regions of interest in 22 participants we identified two main brain network modules, one dorsal and one ventral, and their hub areas: the left dorsolateral prefrontal cortex (dlPFC) and the left medial frontal pole (mFP). These hub areas did not modulate their mutual functional connectivity following sadness but they did so through an interposed area, the subgenual anterior cingulate cortex (sACC). Our results identify dlPFC and mFP as areas regulating interactions between emotional and cognitive networks, and suggest that their modulation by sadness experience is mediated by sACC.

Gardening May Repeatedly Activate the Frontal Pole

Previous epidemiological studies have indicated the effectiveness of gardening and other activities for dementia prevention. Our previous study using near-infrared spectroscopy (NIRS) suggested seeding and watering tasks could induce greater activation than other gardening tasks in the prefrontal area of older adults, but repetitive effects were not fully addressed. The objective of this NIRS study was to investigate the effects of repeated gardening tasks on activation of the frontal pole (FP). We measured oxygenated hemoglobin (Oxy-Hb) values in the FP while 24 healthy right-handed older adults (60 - 73 years) performed a seeding task, a watering task, and a motor programming task (FAB 3) of the Frontal Assessment Battery (FAB). Each task was repeated five times. After the fourth trial, comparison of maximum Oxy-Hb values among the three tasks demonstrated that, in the medial FP, activation during the two gardening tasks was significantly or marginally significantly greater than activation during the FAB 3 task. The results may be attributable to differences in the number of sensory information sources and the number of stimulus-oriented (SO) attention switches and SO thoughts. No significant differences were observed in activation in the lateral FP. Comparison of maximum Oxy-Hb values among five trials within each task showed sustained medial FP activation in all tasks, while the watering task and FAB 3 task showed significantly decreased activation in a portion of the lateral FP. This was possibly due to differences in the number of times switching between SO attention and stimulus-independent (SI) attention, and differences in frequency of changes of visual dimension weighting. Also, in the gardening tasks, the participants needed to respond to changes in the external environment; it can be speculated that the need for collating external information corresponding to changes in the external environment induced repeated FP activation during the gardening tasks.

EP 81. Medial prefrontal aberrations in major depressive disorder revealed by Cytoarchitectonically informed Voxel-based Morphometry

Objective The heterogeneous human frontal pole has been identified as a node in the dysfunctional network of major depressive disorder (MDD) ( Mayberg, 2003 ). The contribution of the medial (socio affective) versus lateral (cognitive) frontal pole to major depression pathogenesis is currently unclear. The authors performed morphometric comparison of the microstructurally informed subdivisions of human frontal pole ( Bludau et al., 2014 ) between depressed patients and comparison subjects using both uni- and multivariate statistics. Method Multisite voxel- and region-based morphometric MRI analysis was conducted in 73 depressed patients and 73 matched comparison subjects without psychiatric history (Gender: Controls [f/m]40/33; Patients [f/m]40/33; chi 2 :1.0, Age: Controls [mean/ SD]38.51/12.56; Patients [mean/SD]41.70/12.95; ttest (p-value): 0.13). Frontal pole volume was first compared between depressed patients and comparison subjects by subdivision-wise classical morphometric analysis. In a second approach, frontal pole volume was compared by subdivision-naive multivariate searchlight analysis based on support vector machines. Results The group comparison showed a significant decrease in volume of the left medial part of the frontal pole (left Fp2) of MDD patients compared to the controls ( Fig. 1 ) ( p r = −0.32)) and within the patients of all sites (Fp2_L ∼ BDI ( r = −0.26)). Duration as well as episodes also correlates negatively with the volume of left Fp2 within the patients (Fp2_L ∼ duration ( r = −0.35); Fp2_L ∼ episodes ( r = −0.34)). Histologically uninformed multivariate voxel-wise statistics provided converging evidence for structural aberrations specific to the microstructurally defined medial area of the frontal pole in depressed patients ( Fig. 2 ). Conclusions Across disparate methods, subregion specificity in the left medial frontal pole volume in depressed patients was demonstrated. Indeed, the frontal pole was shown to structurally and functionally connect to other key regions in major depression pathology, such as the anterior cingulate cortex and the amygdala via the uncinate fasciculus. Present and previous findings consolidate the left medial portion of the frontal pole as particularly altered in major depression.

Medial Prefrontal Aberrations in Major Depressive Disorder Revealed by Cytoarchitectonically Informed Voxel-Based Morphometry.

The heterogeneous human frontal pole has been identified as a node in the dysfunctional network of major depressive disorder. The contribution of the medial (socio-affective) versus lateral (cognitive) frontal pole to major depression pathogenesis is currently unclear. The authors performed morphometric comparison of the microstructurally informed subdivisions of human frontal pole between depressed patients and comparison subjects using both uni- and multivariate statistics. Multisite voxel- and region-based morphometric MRI analysis was conducted in 73 depressed patients and 73 matched comparison subjects without psychiatric history. Frontal pole volume was first compared between depressed patients and comparison subjects by subdivision-wise classical morphometric analysis. In a second approach, frontal pole volume was compared by subdivision-naive multivariate searchlight analysis based on support vector machines. Subdivision-wise morphometric analysis found a significantly smaller medial frontal pole in depressed patients, with a negative correlation of disease severity and duration. Histologically uninformed multivariate voxel-wise statistics provided converging evidence for structural aberrations specific to the microstructurally defined medial area of the frontal pole in depressed patients. Across disparate methods, subregion specificity in the left medial frontal pole volume in depressed patients was demonstrated. Indeed, the frontal pole was shown to structurally and functionally connect to other key regions in major depression pathology, such as the anterior cingulate cortex and the amygdala via the uncinate fasciculus. Present and previous findings consolidate the left medial portion of the frontal pole as particularly altered in major depression.

Connectivity-based parcellation of the human frontal polar cortex.

The frontal pole corresponds to Brodmann area (BA) 10, the largest single architectonic area in the human frontal lobe. Generally, BA10 is thought to contain two or three subregions that subserve broad functions such as multitasking, social cognition, attention, and episodic memory. However, there is a substantial debate about the functional and structural heterogeneity of this large frontal region. Previous connectivity-based parcellation studies have identified two or three subregions in the human frontal pole. Here, we used diffusion tensor imaging to assess structural connectivity of BA10 in 35 healthy subjects and delineated subregions based on this connectivity. This allowed us to determine the correspondence of structurally based subregions with the scheme previously defined functionally. Three subregions could be defined in each subject. However, these three subregions were not spatially consistent between subjects. Therefore, we accepted a solution with two subregions that encompassed the lateral and medial frontal pole. We then examined resting-state functional connectivity of the two subregions and found significant differences between their connectivities. The medial cluster was connected to nodes of the default-mode network, which is implicated in internally focused, self-related thought, and social cognition. The lateral cluster was connected to nodes of the executive control network, associated with directed attention and working memory. These findings support the concept that there are two major anatomical subregions of the frontal pole related to differences in functional connectivity.Electronic supplementary materialThe online version of this article (doi:10.1007/s00429-014-0809-6) contains supplementary material, which is available to authorized users.

Neuroscience in branding: A functional magnetic resonance imaging study on brands’ implicit and explicit impressions

Although the use of neuroscientific knowledge to investigate marketing issues has been widely discussed, to date, few empirical studies have been published. This study is a first approach in the development of a theory of the perception of brands, which is based on neuroscience. In a Functional Magnetic Resonance Imaging experiment, we stimulated participants with commercial brands’ logos, with and without explicit instructions on how to assess them, in an attempt to capture the real-life experience of evaluating brands. We found common activations in both situations in the medial frontal pole, the paracingulate gyrus, the frontal orbital cortex, the frontal medial cortex, and in the hippocampus. In a general scheme of brands’ perception, we hypothesised a relationship between Theory of Mind and meta-representations, in particular self-reflexive ones: ‘I think about what others are thinking about me’. We suggest that brands have an important social dimension. Brands may function like a social currency, which every individual uses to assess others, and which others are expected to use in their assessments of the individual. Brands are most probably social tools.

Neural correlates of the emotional and symbolic content of brands: A neuroimaging study

Brands are believed to embody emotional, socially relevant and self-related content. In this experiment functional magnetic resonance imaging (fMRI) was used to explore the neural correlates of brands' perception. A common network of brain areas involved in the assessment of brands was found, and brain structures that activated significantly more with positive brands than indifferent ones. The participation of the emotional system was remarkable: every brand was felt in order to be assessed; however only preferred brands activated brain regions supposed to be emotional inducers. There were also activations in the paracingulate gyrus and temporo-parietal junction, brain regions believed to be involved in Theory of Mind. Once more, brands rated as positive elicited activations in the ventral medial frontal pole, which may be attributed to self-relatedness and to the role of brands in self-construal.

Endogenous cortisol is associated with functional connectivity between the amygdala and medial prefrontal cortex

Whether glucocorticoids mediate medial prefrontal cortex (mPFC) regulation of the amygdala in humans remains unclear. In the current study we investigated whether cortisol levels under relatively stress-free circumstances are related to amygdala resting-state functional connectivity with the mPFC. Resting-state fMRI data were acquired from 20 healthy male participants. Salivary cortisol was sampled at multiple times throughout the experiment. The cortisol area under the curve increase (AUCi) was calculated as a measure of cortisol dynamics. Next, seed based correlations were employed on the resting-state fMRI data to reveal regions of amygdala functional connectivity related to variations in cortisol AUCi. The resulting statistical maps were corrected for multiple comparisons using cluster based thresholding (Z>2.3, p<.05). Two regions in the mPFC showed decreasing negative functional connectivity with the amygdala when a lesser decrease in cortisol AUCi was observed: the perigenual anterior cingulate cortex and medial frontal pole (BA10). Although we initially showed a relation with cortisol AUCi, it seemed that the baseline cortisol levels were actually driving this effect: higher baseline cortisol levels related to stronger negative functional connectivity with the mPFC. Endogenous cortisol levels may modulate amygdala functional connectivity with specific regions in the mPFC, even under relatively stress-free circumstances. Our results corroborate previous findings from both animal and human studies, suggesting cortisol-mediated regulation of the amygdala by the mPFC. We propose that through this feedback mechanism the stress response might be adjusted, pointing to the putative role of cortisol in modulating stress- and, more generally, emotional responses.

Detecting sarcasm from paralinguistic cues: Anatomic and cognitive correlates in neurodegenerative disease

While sarcasm can be conveyed solely through contextual cues such as counterfactual or echoic statements, face-to-face sarcastic speech may be characterized by specific paralinguistic features that alert the listener to interpret the utterance as ironic or critical, even in the absence of contextual information. We investigated the neuroanatomy underlying failure to understand sarcasm from dynamic vocal and facial paralinguistic cues. Ninety subjects (20 frontotemporal dementia, 11 semantic dementia [SemD], 4 progressive non-fluent aphasia, 27 Alzheimer's disease, 6 corticobasal degeneration, 9 progressive supranuclear palsy, 13 healthy older controls) were tested using the Social Inference — Minimal subtest of The Awareness of Social Inference Test (TASIT). Subjects watched brief videos depicting sincere or sarcastic communication and answered yes–no questions about the speaker's intended meaning. All groups interpreted Sincere (SIN) items normally, and only the SemD group was impaired on the Simple Sarcasm (SSR) condition. Patients failing the SSR performed more poorly on dynamic emotion recognition tasks and had more neuropsychiatric disturbances, but had better verbal and visuospatial working memory than patients who comprehended sarcasm. Voxel-based morphometry analysis of SSR scores in SPM5 demonstrated that poorer sarcasm comprehension was predicted by smaller volume in bilateral posterior parahippocampi (PHc), temporal poles, and R medial frontal pole (pFWE<0.05). This study provides lesion data suggesting that the PHc may be involved in recognizing a paralinguistic speech profile as abnormal, leading to interpretive processing by the temporal poles and right medial frontal pole that identifies the social context as sarcastic, and recognizes the speaker's paradoxical intentions.

The neural system that bridges reward and cognition in humans: an fMRI study.

We test the hypothesis that motivational and cognitive processes are linked by a specific neural system to reach maximal efficiency. We studied six normal subjects performing a working memory paradigm (n-back tasks) associated with different levels of monetary reward during an fMRI session. The study showed specific brain activation in relation with changes in both the cognitive loading and the reward associated with task performance. First, the working memory tasks activated a network including the dorsolateral prefrontal cortex [Brodmann area (BA) 9/46] and, in addition, in the lateral frontopolar areas (BA 10), but only in the more demanding condition (3-back task). This result suggests that lateral prefrontal areas are organized in a caudo-rostral continuum in relation with the increase in executive requirement. Second, reward induces an increased activation in the areas already activated by working memory processing and in a supplementary region, the medial frontal pole (BA 10), regardless of the level of cognitive processing. It is postulated that the latter region plays a specific role in monitoring the reward value of ongoing cognitive processes. Third, we detected areas where the signal decreases (ventral-BA 11/47 and subgenual prefrontal cortices) in relation with both the increase of cognitive demand and the reward. The deactivation may represent an emotional gating aimed at inhibiting adverse emotional signals to maximize the level of performance. Taken together, these results suggest a balance between increasing activity in cortical cognitive areas and decreasing activity in the limbic and paralimbic structures during ongoing higher cognitive processing.