Temporoparietal Research Articles

The effects of right temporoparietal junction stimulation on embodiment, presence, and performance in teleoperation.

Embodiment (the sensation that arises when the properties of an external instrument are processed as if they are the attributes of one's own biological body) and (tele)presence (the sensation of being fully engaged and immersed in a location other than the physical space occupied by one's body) sustain the perception of the physical self and potentially improve performance in teleoperations (a system that enables human intelligence to control robots and requires implementing an effective human-machine interface). Embodiment and presence may be interdependent and influenced by right temporo-parietal junction (rTPJ) activity. We investigated the interplay between embodiment, (tele)presence, and performance in teleoperation, focusing on the role of the rTPJ. Participants underwent a virtual reality task with transcranial direct current stimulation (tDCS) twice, receiving either active or sham stimulation. Behavioral measures (driving inaccuracy, elapsed time in the lap, time spent in attentional lapses, short-term self-similarity, and long-term self-similarity), perceived workload (mental demand, physical demand, temporal demand, own performance, effort, and frustration), embodiment's components (ownership, agency, tactile sensations, location, and external appearance), and presence's components (realism, possibility to act, quality of interface, possibility to examine, self-evaluation of performance, haptic, and sounds) were assessed. The results showed that rTPJ stimulation decreased perceived ownership but enhanced presence with changes in the complexity of visuomotor adjustments (long and short-term self-similarity indices). Structural equation modeling revealed that embodiment increased visuomotor inaccuracy (a composite variable of overall performance, including deviations from the optimal trajectory and the time taken to complete the task), presence reduced workload, and workload increased inaccuracy. These results suggested a dissociation between embodiment and presence, with embodiment hindering performance. Prioritizing virtual integration may lower human performance, while reduced workload from presence could aid engagement. These findings emphasize the intricate interplay between rTPJ, subjective experiences, and performance in teleoperation.

Neural Correlates of Positive Outcome Expectancy for Aggression: Evidence from Voxel-Based Morphometry and Resting-State Functional Connectivity Analysis.

Positive outcome expectancy is a crucial cognitive factor influencing aggression, yet its neural basis remains unclear. Therefore, the present study combined voxel-based morphometry (VBM) with a resting-state functional connectivity (RSFC) analysis to investigate the brain correlates of positive outcome expectancy in aggression in young people. In the VBM analysis, multiple linear regression was conducted to explore the relationship between individual differences in aggressive positive outcome expectancy and regional gray matter volume (GMV) among 325 undergraduate students. For the RSFC analysis, seed regions were selected based on the results of the VBM analysis. Subsequently, multiple linear regression was employed to examine whether a significant correlation existed between individual differences in aggressive positive outcome expectancy and the RSFC of seed regions with other brain regions in 304 undergraduate students. The findings indicated that aggressive positive outcome expectancy was positively correlated with GMV in the posterior cingulate cortex (PCC), right temporoparietal junction (TPJ), and medial prefrontal cortex (MPFC). Moreover, it was also positively associated with RSFC between the PCC and the left dorsolateral prefrontal cortex (DLPFC). The prediction analysis indicated robust relationships between aggressive positive outcome expectancy and the GMV in the PCC, right TPJ, as well as the RSFC between the PCC and the left DLPFC. Our research provides the initial evidence for the neural basis of positive outcome expectancy in aggression, suggesting the potential role of the PCC as a hub in its neural network.

Neural correlates of empathy in mild cognitive impairment.

The occurrence of clinically significant changes in empathy is a matter of debate in Alzheimer's disease (AD). Altered empathic mechanisms observed in AD may be a consequence of cognitive impairment, more specifically of reduced mental flexibility and self-regulation. The present study explored possible changes in empathy for subjects in the prodromal phase of AD, namely mild cognitive impairment (MCI) due to AD, and of their neural substrates. Eighteen MCI patients and 20 healthy controls (HC) were included in the study. The Interpersonal Reactivity Index (IRI) questionnaire was administered to each participant. The IRI encompasses four factors: Perspective Taking; Fantasy; Empathic Concern; Personal Distress. MCI patients underwent a magnetic resonance imaging structural examination and were compared to 30 healthy controls (HC-MRI). A limited number of cortical and subcortical regions involved in social cognition was selected as regions of interest (ROIs). MCI individuals obtained lower scores than HC in the Perspective Taking and Fantasy subscales of the IRI, whereas they obtained higher scores on Empathic Concern. Regarding neuroimaging data, a significant correlation emerged between IRI scores and the neural measurements of different regions involved in empathy, especially covering the temporoparietal junction, which is a critical region engaged in both affective and cognitive dimensions of empathy. The results of the present study suggest that a subtle impairment in regulatory mechanisms of empathy may occur very early during the course of AD, possibly as a consequence of neuropathological changes occurring in brain regions involved in social cognition.

A Causal Role of Right Temporoparietal Junction in Prosocial Learning: A Transcranial Direct Current Stimulation Study

Prosocial behavior is a common and important aspect of everyday social life. To behave prosocially, we need to learn the consequences of our actions for other people, known as prosocial learning. Previous studies have identified the right temporoparietal junction (rTPJ) as the critical neurological substrate for prosocial behavior. However, little is known about the causal role of the rTPJ in prosocial learning. To clarify the role of the rTPJ in prosocial learning, we used a reinforcement learning paradigm and transcranial direct current stimulation (tDCS). A total of 75 participants were recruited and randomly assigned to the anodal or sham tDCS group. While receiving tDCS stimulation over the rTPJ, participants were instructed to choose between different stimuli that were probabilistically associated with rewards for themselves in the self-learning condition or for another person in the prosocial-learning condition. Participants were able to learn to obtain rewards for themselves or others, and learning performance in the self-learning condition was better than that in the prosocial-learning condition. However, anodal tDCS over the rTPJ significantly improved learning performance in the prosocial-learning condition. These results indicate that the rTPJ plays a causal role in prosocial learning.

Mechanistic account of the left auditory cortex for tone-matching in schizophrenia: A pilot transcranial random noise stimulation (tRNS) sham-controlled study

ObjectiveDeficits in the ability to match tones following brief delay and their contribution to higher-order cognitive alterations have been repeatedly documented in schizophrenia. The aim was to explore if left fronto-temporal high-frequency transcranial random noise stimulation (hf-tRNS), with electrodes placed over brain regions involved in tone-matching would significantly modulate performances in participants with schizophrenia. MethodsIn a randomized, double-blind sham-controlled study, 10 participants with schizophrenia were allocated to receive ten sessions of either active or sham hf-tRNS. The anode was placed over the left prefrontal cortex and the cathode over the left temporoparietal junction. A tone-matching task was administered before and after the hf-tRNS. ResultsWe calculated the changes in tone-matching performance before and after hf-tRNS session in each group. A significant between-group difference was observed for the difficult tone-matching conditions (W= 14.500, p = 0.032), with tone-matching improvement in the sham group and no improvement in the active group. Discussionhf-tRNS could disrupt the test-retest learning effect in the tone-matching task in individuals with schizophrenia. It is likely that this disruption resulted from cathodal-induced inhibition of the functional coupling between auditory cortical areas that correlates with tone-matching performance in patients. ConclusionThe findings contribute to our understanding of hf-tRNS effects on early auditory processing in schizophrenia.

Brain stimulation targets for chronic pain: Insights from meta-analysis, functional connectivity and literature review

Noninvasive brain stimulation (NIBS) techniques have demonstrated their potential for chronic pain management, yet their efficacy exhibits variability across studies. Refining stimulation targets and exploring additional targets offer a possible solution to this challenge. This study aimed to identify potential brain surface targets for NIBS in treating chronic pain disorders by integrating literature review, neuroimaging meta-analysis, and functional connectivity analysis on 90 chronic low back pain patients. Our results showed that the primary motor cortex (M1) (C3/C4, 10–20 EEG system) and prefrontal cortex (F3/F4/Fz) were the most used brain stimulation targets for chronic pain treatment according to the literature review. The bilateral precentral gyrus (M1), supplementary motor area, Rolandic operculum, and temporoparietal junction, were all identified as common potential NIBS targets through both a meta-analysis sourced from Neurosynth and functional connectivity analysis. This study presents a comprehensive summary of the current literature and refines the existing NIBS targets through a combination of imaging meta-analysis and functional connectivity analysis for chronic pain conditions. The derived coordinates (with integration of the international electroencephalography (EEG) 10/20 electrode placement system) within the above brain regions may further facilitate the localization of these targets for NIBS application. Our findings may have the potential to expand NIBS target selection beyond current clinical trials and improve chronic pain treatment.

Mother-infant social gaze dynamics relate to infant brain activity and word segmentation

The ‘social brain’, consisting of areas sensitive to social information, supposedly gates the mechanisms involved in human language learning. Early preverbal interactions are guided by ostensive signals, such as gaze patterns, which are coordinated across body, brain, and environment. However, little is known about how the infant brain processes social gaze in naturalistic interactions and how this relates to infant language development. During free-play of 9-month-olds with their mothers, we recorded hemodynamic cortical activity of ´social brain` areas (prefrontal cortex, temporo-parietal junctions) via fNIRS, and micro-coded mother’s and infant’s social gaze. Infants’ speech processing was assessed with a word segmentation task. Using joint recurrence quantification analysis, we examined the connection between infants’ ´social brain` activity and the temporal dynamics of social gaze at intrapersonal (i.e., infant’s coordination, maternal coordination) and interpersonal (i.e., dyadic coupling) levels. Regression modeling revealed that intrapersonal dynamics in maternal social gaze (but not infant’s coordination or dyadic coupling) coordinated significantly with infant’s cortical activity. Moreover, recurrence quantification analysis revealed that intrapersonal maternal social gaze dynamics (in terms of entropy) were the best predictor of infants’ word segmentation. The findings support the importance of social interaction in language development, particularly highlighting maternal social gaze dynamics.

Neural Correlates of Social Decision-Making.

Objective: Recent studies have utilized innovative techniques to investigate the neural mechanisms underlying social and individual decision-making, aiming to understand how individuals respond to the world. Method : In this review, we summarized current scientific evidence concerning the neural underpinnings of social decision-making and their impact on social behavior. Results: Critical brain regions involved in social cognition and decision-making are integral to the process of social decision-making. Notably, the medial prefrontal cortex (mPFC) and temporoparietal junction (TPJ) contribute to the comprehension of others' mental states. Similarly, the posterior superior temporal sulcus (pSTS) shows heightened activity when individuals observe faces and movements. On the lateral surface of the brain, the inferior frontal gyrus (IFG) and inferior parietal sulcus (IPS) play a role in social cognition. Furthermore, the medial surface of the brain, including the amygdala, anterior cingulate cortex (ACC), and anterior insula (AI), also participates in social cognition processes. Regarding decision-making, functional magnetic resonance imaging (fMRI) studies have illuminated the involvement of a network of brain regions, encompassing the ventromedial prefrontal cortex (vmPFC), ventral striatum (VS), and nucleus accumbens (NAcc). Conclusion: Dysfunction in specific subregions of the prefrontal cortex (PFC) has been linked to various psychiatric conditions. These subregions play pivotal roles in cognitive, emotional, and social processing, and their impairment can contribute to the development and manifestation of psychiatric symptoms. A comprehensive understanding of the unique contributions of these PFC subregions to psychiatric disorders has the potential to inform the development of targeted interventions and treatments for affected individuals.

The role of prefrontal cortex and temporoparietal junction in interpersonal comfort and emotional approach

Our perception of physical distance to individuals and stimuli is influenced by our mental distance and relatedness. The present study aimed to investigate the role of the dorsolateral prefrontal cortex (dlPFC), ventromedial prefrontal cortex (vmPFC), and right temporoparietal junction (rTPJ) in interpersonal comfortable distance and approach behaviors towards emotional stimuli. Twenty healthy volunteers received brain stimulation in four separate sessions with a one-week interval, including anodal left dlPFC, anodal right vmPFC, anodal rTPJ, and sham condition, with an extracranial return electrode. Our results revealed an increase in interpersonal distance during anodal rTPJ stimulation and a decrease in distance to positive pictures during anodal vmPFC stimulation. These findings suggest that the rTPJ plays a role in the perceptual component of self-other distancing, while the vmPFC is involved in approaching positive emotions.

Identifying Cognitive Resilience Related Genes Among Genetic Risk Loci of Alzheimer’s Disease

AbstractBackgroundCognitive resilience (CR) in the context of Alzheimer’s disease (AD) describes the ability to maintain cognitive function despite the presence of neuropathology (Hohman et al., 2016). While most studies have focused on investigating genetic risk factors for developing AD, we here examined the association of most robust risk loci (Bellenguez et al., 2021) with CR using a neuroimaging‐based approach that incorporates measures of brain atrophy and cognition into a quantitative CR metric (van Loenhoud, 2017).MethodWe performed magnetic resonance imaging (3T) and DNA testing on n = 440 amyloid‐positive individuals in different clinical stages of AD. Employing a global cognitive composite score, we predicted gray matter volume (GM) in each voxel, adjusted for sex, age, premorbid intracranial volume, disease stage, and scanner type. To operationalize CR, W‐scores were computed for each individual based on the standardized individual difference between predicted and observed GM within temporoparietal (TP) and whole brain (WB) masks. In this approach, positive W‐scores reflect low CR, while negative W‐scores reflect high CR. A total of 83 genetic risk variants for AD (Bellenguez et al., 2021) were each tested for their association with W‐scores in a linear regression model corrected for population substructure (PC1‐5).ResultWe found an association for 6 genetic loci, of which variants rs113706587 in gene RASGEF1c and rs6943429 in gene UMAD1 were associated with higher CR (TP: p<0.01, p<0.02; WB: p<0.02, p<0.01). As expected, APOEe4 was associated with low CR (TP: p<0.01, WB: p<0.01), as were genetic markers of genes CLU, MINDY2 (WB: p<0.04, p<0.04), and BCKDK (WB: p<0.05, TP: p<0.04). Importantly, no association was found between APOEe2 and CR (WB: p = 0.195, TP: p = 0.139).ConclusionAmong genetic risk‐loci for AD, we identified two genetic variants associated with cognitive resilience in amyloid‐positive individuals. Interestingly, APOEe4 associated with low CR, as did genes CLU, MINDY2, and BCKDK, indicating anti‐resilience – possibly through accelerating mechanisms. In addition, our results suggest that CR against AD is independent of the protective relationship found between APOEe2 and developing AD, highlighting the relevance of investigating the mechanisms behind CR.

A CenTauR scale based on 18F‐MK6240

AbstractBackgroundA standardized scale for the quantification of tau PET imaging would allow comparison and combination of data across tracers and sites resulting in large meta‐analysis and the application of universal cut‐offs. The proposed approach called CenTauR (CTR) was evaluated on 18F‐MK6240 using both global and regional anchoring.Method375 18F‐MK6240 PET & T1w scan pairs (HC Aß‐ = 179/MCI Aß+ = 98/AD Aß+ = 98) from AIBL&ADNeT were spatially normalised using SPM8 and SUVR normalised using the cerebellar cortex. PET scans were then quantified in 4 composite ROIs [Mesial‐Temporal (Me), Meta‐Temporal (MT), Temporo‐Parietal (TP) and Frontal (FT)] from a previously defined “universal” cortical mask. To anchor the 0 and 100 CTR, we only included HC Aß‐ (<10CL) and AD Aß+ (>25CL) individuals younger than 75y, with MMSE = 20, we also excluded HC participants with a quantification higher than the 75%tile in the Me and AD patients with a quantification lower than the 25%tile in the MT, resulting in 68 HC Aß‐ and 29 AD Aß+. We investigated two CTR scaling approaches using either a single transform based on the TP anchors to transform SUVR into CTR for all composites or using region‐based equations scaled with regional anchors.ResultThe mean and standard deviation (std) for the HC and AD groups are reported in Table 1. Using a single transformation resulted in the following equation: Ct = 100x(SUVR‐0.97)/2.26 Region‐based equations can be extrapolated from Table 1. Figures 1 and 2 show that regional CTR overstretches quantification in FT compared to single equation‐derived CTR. Thresholds set at 2 std above the HC were 2.38, 9.43, 7.66, 1.82, and 6.16 CTR for Me, MT, TP, FT and Global respectively, and were 7.05, 7.48, 7.66, 10.20, 7.68 CTR when using regional equation‐derived CTR.ConclusionThe region‐based approach provided slightly more consistent CTR distributions in the HC across the ROIs however, this approach tends to over‐stretch the CTR values in the frontal region.

A CenTauR scale based on 18F‐MK6240

AbstractBackgroundA standardized scale for the quantification of tau PET imaging would allow comparison and combination of data across tracers and sites resulting in large meta‐analysis and the application of universal cut‐offs. The proposed approach called CenTauR (CTR) was evaluated on 18F‐MK6240 using both global and regional anchoring.Method375 18F‐MK6240 PET & T1w scan pairs (HC Aβ‐ = 179/MCI Aβ+ = 98/AD Aβ+ = 98) from AIBL&ADNeT were spatially normalised using SPM8 and SUVR normalised using the cerebellar cortex. PET scans were then quantified in 4 composite ROIs [Mesial‐Temporal (Me), Meta‐Temporal (MT), Temporo‐Parietal (TP) and Frontal (FT)] from a previously defined “universal” cortical mask. To anchor the 0 and 100 CTR, we only included HC Aβ‐ (<10CL) and AD Aβ+ (>25CL) individuals younger than 75y, with MMSE ≥20, we also excluded HC participants with a quantification higher than the 75%tile in the Me and AD patients with a quantification lower than the 25%tile in the MT, resulting in 68 HC Aβ‐ and 29 AD Aβ+. We investigated two CTR scaling approaches using either a single transform based on the TP anchors to transform SUVR into CTR for all composites or using region‐based equations scaled with regional anchors.ResultThe mean and standard deviation (std) for the HC and AD groups are reported in Table 1.Using a single transformation resulted in the following equation:Ct = 100x(SUVR‐0.97)/2.26Region‐based equations can be extrapolated from Table 1. Figures 1 and 2 show that regional CTR overstretches quantification in FT compared to single equation‐derived CTR. Thresholds set at 2 std above the HC were 2.38, 9.43, 7.66, 1.82, and 6.16 CTR for Me, MT, TP, FT and Global respectively, and were 7.05, 7.48, 7.66, 10.20, 7.68 CTR when using regional equation‐derived CTR.ConclusionThe region‐based approach provided slightly more consistent CTR distributions in the HC across the ROIs however, this approach tends to over‐stretch the CTR values in the frontal region.

Uncovering individual variations in bystander intervention of injustice through intrinsic brain connectivity patterns

When confronted with injustice, individuals often intervene as third parties to restore justice by either punishing the perpetrator or helping the victim, even at their own expense. However, little is known about how individual differences in third-party intervention propensity are related to inter-individual variability in intrinsic brain connectivity patterns and how these associations vary between help and punishment intervention. To address these questions, we employed a novel behavioral paradigm in combination with resting-state fMRI and inter-subject representational similarity analysis (IS-RSA). Participants acted as third-party bystanders and needed to decide whether to maintain the status quo or intervene by either helping the disadvantaged recipient (Help condition) or punishing the proposer (Punish condition) at a specific cost. Our analyses focused on three brain networks proposed in the third-party punishment (TPP) model: the salience (e.g., dorsal anterior cingulate cortex, dACC), central executive (e.g., dorsolateral prefrontal cortex, dlPFC), and default mode (e.g., dorsomedial prefrontal cortex, dmPFC; temporoparietal junction, TPJ) networks. IS-RSA showed that individual differences in resting-state functional connectivity (rs-FC) patterns within these networks were associated with the general third-party intervention propensity. Moreover, rs-FC patterns of the right dlPFC and right TPJ were more strongly associated with individual differences in the helping propensity rather than the punishment propensity, whereas the opposite pattern was observed for the dmPFC. Post-hoc predictive modeling confirmed the predictive power of rs-FC in these regions for intervention propensity across individuals. Collectively, these findings shed light on the shared and distinct roles of key regions in TPP brain networks at rest in accounting for individual variations in justice-restoring intervention behaviors.

Cognitive analysis based on EEG measurements on children with stunting-indicated in East Nusa Tenggara

Children with stunting have been associated with delayed brain development and poor cognitive performance by a lack of attentional control. The aim of the present study was to determine characteristics of stunting children based on theta (4-8 Hz), alpha (8-12 Hz) and beta (12-30 Hz) oscillation at anterofrontal (AF) and temporoparietal (TP). This research involved two groups: Stunting Group (SG, N=14) and Control Group (C; N=8) from East Nusa Tenggara. EEG was recorded during an eyes-open condition at baseline and puzzle task. Our result revealed alteration of theta oscillation in SG AF8 and TP10 during puzzle task, supporting role of theta oscillation in higher working memory loads although it was not accompanied by proper TP connectivity. Higher alpha and beta AF7 activity in SG compared to control group implying decreasing attentional processing and higher arousal. According to Laterality Index (LI), we revealed alteration in temporoparietal SG during puzzle task. These findings provide new insights about theta, alpha, and beta oscillation in stunting children may reflect that declining attentional functioning during the puzzle task leads to poor cognitive performance.

Neural Mechanisms Underlying Trust to Friends, Community Members, and Unknown Peers in Adolescence.

Trust plays an important role during adolescence for developing social relations. Although prior developmental studies give us insight into adolescents' development of differentiation between close (e.g., friends) and unknown (e.g., unknown peers) targets in trust choices, less is known about the development of trust to societal targets (e.g., members of a community organization) and its underlying neural mechanisms. Using a modified version of the Trust Game, our preregistered fMRI study examined the underlying neural mechanisms of trust to close (friend), societal (community member), and unknown others (unknown peer) during adolescence in 106 participants (aged 12-23 years). Adolescents showed most trust to friends, less trust to community members, and the least trust to unknown peers. Neural results show that target differentiation in adolescents' trust behavior is associated with activity in social brain regions implicated during mentalizing, reward processing, and cognitive control. Recruitment of the medial prefrontal cortex (mPFC) and OFC was higher for closer targets (i.e., friend and community member). For the mPFC, this effect was most pronounced during no trust choices. Trust to friends was additionally associated with increased activity in the precuneus and bilateral temporal parietal junction. In contrast, bilateral dorsolateral prefrontal cortex and anterior cingulate cortex were most active for trust to unknown peers. The mPFC showed increased activity with age and consistent relations with individual differences in feeling needed/useful.

Data‐driven neuroanatomical subtype trajectories of primary progressive aphasia

AbstractBackgroundPrimary progressive aphasia (PPA) is an atypical neurodegenerative dementia with three main clinical variants: semantic (svPPA), non‐fluent/agrammatic (nfvPPA) and logopenic (lvPPA). While svPPA is typically associated with left anterior temporal lobe atrophy, neuroimaging findings in nfvPPA, lvPPA and PPA not otherwise specified (PPA‐nos) are more variable. We therefore applied unsupervised machine learning to one of the largest databases of PPA magnetic resonance imaging (MRI) scans ever acquired.MethodBaseline MRI scans were collected from 273 people with PPA participating in the longitudinal research programme in the Queen Square Dementia Research Centre (svPPA n = 97; nfvPPA n = 109; lvPPA n = 51; PPA‐nos n = 16). Longitudinal scans were collected from 138 participants. We used Subtype and Stage Inference (SuStaIn), a model that combines disease progression modelling with unsupervised machine learning to identify subgroups of patients following a similar trajectory. We standardised the data with respect to cognitively normal controls (n = 360). Based on clinicians’ input we chose 19 brain regions of interest to model from those generated by GIF (Cardoso et al. 2012). The model was fit using baseline data, selecting the appropriate number of subtypes using cross‐validation (Young et al. 2018).ResultCross‐validation supported four subtypes of spatiotemporal atrophy (Figure 1). Clinical variant representation per subtype assignment (1/2/3/4) was: svPPA (n = 74/15/4/4), nfvPPA (n = 3/35/21/44), lvPPA (n = 1/18/30/2) and PPA‐nos (n = 7/4/3/2) (Figure 2). Subtype 1 showed early decline in the left anterior temporal lobe and sparing of the left frontal lobe. Subtype 2 showed early decline of the left insula and sparing of the temporal pole. Subtype 3 showed initial atrophy of the left temporoparietal junction; Subtype 4 showed early atrophy in the left precentral gyrus. Statistical analysis of posterior distributions found low similarity between subtypes (Hellinger distance > 0.66) (Figure 3), validating the presence of four distinct subtypes.ConclusionWhile the data‐driven atrophy subtypes did not align perfectly with clinical variants, we found a correspondence between Subtype 1 and svPPA, the most coherent PPA variant. Subtypes 2,3 and 4 were associated with nfvPPA and lvPPA, corroborating work suggesting these diagnostic terms encompass multiple clinical phenotypes. Future work will investigate the association between clinical diagnosis, longitudinal subtype, and clinical measures.

Data‐driven neuroanatomical subtype trajectories of primary progressive aphasia

AbstractBackgroundPrimary progressive aphasia (PPA) is an atypical neurodegenerative dementia with three main clinical variants: semantic (svPPA), non‐fluent/agrammatic (nfvPPA) and logopenic (lvPPA). While svPPA is typically associated with left anterior temporal lobe atrophy, neuroimaging findings in nfvPPA, lvPPA and PPA not otherwise specified (PPA‐nos) are more variable. We therefore applied unsupervised machine learning to one of the largest databases of PPA magnetic resonance imaging (MRI) scans ever acquired.MethodBaseline MRI scans were collected from 273 people with PPA participating in the longitudinal research programme in the Queen Square Dementia Research Centre (svPPA n = 97; nfvPPA n = 109; lvPPA n = 51; PPA‐nos n = 16). Longitudinal scans were collected from 138 participants. We used Subtype and Stage Inference (SuStaIn), a model that combines disease progression modelling with unsupervised machine learning to identify subgroups of patients following a similar trajectory. We standardised the data with respect to cognitively normal controls (n = 360). Based on clinicians’ input we chose 19 brain regions of interest to model from those generated by GIF (Cardoso et al. 2012). The model was fit using baseline data, selecting the appropriate number of subtypes using cross‐validation (Young et al. 2018).ResultCross‐validation supported four subtypes of spatiotemporal atrophy (Figure 1). Clinical variant representation per subtype assignment (1/2/3/4) was: svPPA (n = 74/15/4/4), nfvPPA (n = 3/35/21/44), lvPPA (n = 1/18/30/2) and PPA‐nos (n = 7/4/3/2) (Figure 2). Subtype 1 showed early decline in the left anterior temporal lobe and sparing of the left frontal lobe. Subtype 2 showed early decline of the left insula and sparing of the temporal pole. Subtype 3 showed initial atrophy of the left temporoparietal junction; Subtype 4 showed early atrophy in the left precentral gyrus. Statistical analysis of posterior distributions found low similarity between subtypes (Hellinger distance > 0.66) (Figure 3), validating the presence of four distinct subtypes.ConclusionWhile the data‐driven atrophy subtypes did not align perfectly with clinical variants, we found a correspondence between Subtype 1 and svPPA, the most coherent PPA variant. Subtypes 2,3 and 4 were associated with nfvPPA and lvPPA, corroborating work suggesting these diagnostic terms encompass multiple clinical phenotypes. Future work will investigate the association between clinical diagnosis, longitudinal subtype, and clinical measures.

Characterizing EEG signals of meditative states using persistent homology and Hodge spectral entropy

We present a novel topological characterization of EEG time series signals associated with two meditative states: autobiographical self-reflection and mantra-based meditation. The results demonstrate significant information geometric differences among the two groups of meditators and the control group for two brain regions, namely anterior frontal (AF) and temporoparietal (TP). The analysis involves global topological invariants and persistent homology features of the point cloud data constructed from the EEG time series using Takens’s embedding. While traditional EEG analyses face the well-known issues of noise and artefacts, the persistent homology approach is robust to them due to its emphasis on the overall topological changes rather than the transient structures. We analyse the characteristics of the Betti areas, peak location of Betti curves, persistent entropy, persistent amplitude and Hodge spectral entropy of the meditative states for up to the second homology dimension. We find that the mantra- based meditative state is rich in persistent features compared to autobiographical self-reflection. Also, the entropic measures indicate reduced chaotic dynamics and enhanced topological structure formation for the former. Moreover, the correlation of Hodge spectral entropy with persistent entropy or Betti area in a group is a key feature in differentiating the TP and AF channels. These topological features can be used to classify the meditative states with more than 95% accuracy.

Transcranial direct current stimulation of the right temporoparietal junction facilitates hippocampal spatial learning in Alzheimer’s disease and mild cognitive impairment

ObjectiveSpatial memory deficits are an early symptom in Alzheimer’s disease (AD), reflecting the neurodegenerative processes in the neuronal navigation network such as in hippocampal and parietal cortical areas. As no effective treatment options are available, neuromodulatory interventions are increasingly evaluated. Against this backdrop, we investigated the neuromodulatory effect of anodal transcranial direct current stimulation (tDCS) on hippocampal place learning in patients with AD or mild cognitive impairment (MCI). MethodsIn this randomized, double-blind, sham-controlled study with a cross-over design anodal tDCS of the right temporoparietal junction (2 mA for 20 minutes) was applied to 20 patients diagnosed with AD or MCI and in 22 healthy controls while they performed a virtual navigation paradigm testing hippocampal place learning. ResultsWe show an improved recall performance of hippocampal place learning after anodal tDCS in the patient group compared to sham stimulation but not in the control group. ConclusionsThese results suggest that tDCS can facilitate spatial memory consolidation via stimulating the parietal-hippocampal navigation network in AD and MCI patients. SignificanceOur findings suggest that tDCS of the temporoparietal junction may restore spatial navigation and memory deficits in patients with AD and MCI.

Lower cortical thickness and increased brain aging in adults with cocaine use disorder.

Cocaine use disorder (CUD) is a global health issue with severe behavioral and cognitive sequelae. While previous evidence suggests a variety of structural and age-related brain changes in CUD, the impact on both, cortical thickness and brain age measures remains unclear. Derived from a publicly available data set (SUDMEX_CONN), 74 CUD patients and 62 matched healthy controls underwent brain MRI and behavioral-clinical assessment. We determined cortical thickness by surface-based morphometry using CAT12 and Brain Age Gap Estimate (BrainAGE) via relevance vector regression. Associations between structural brain changes and behavioral-clinical variables of patients with CUD were investigated by correlation analyses. We found significantly lower cortical thickness in bilateral prefrontal cortices, posterior cingulate cortices, and the temporoparietal junction and significantly increased BrainAGE in patients with CUD [mean (SD) = 1.97 (±3.53)] compared to healthy controls (p < 0.001, Cohen's d = 0.58). Increased BrainAGE was associated with longer cocaine abuse duration. Results demonstrate structural brain abnormalities in CUD, particularly lower cortical thickness in association cortices and dose-dependent, increased brain age.