Two distinct networks for encoding goals and forms of action: An effective connectivity study.

Goal-directed actions are characterized by two main features: the content (i.e., the action goal) and the form, called vitality forms (VF) (i.e., how actions are executed). It is well established that both the action content and the capacity to understand the content of another's action are mediated by a network formed by a set of parietal and frontal brain areas. In contrast, the neural bases of action forms (e.g., gentle or rude actions) have not been characterized. However, there are now studies showing that the observation and execution of actions endowed with VF activate, in addition to the parieto-frontal network, the dorso-central insula (DCI). In the present study, we established-using dynamic causal modeling (DCM)-the direction of information flow during observation and execution of actions endowed with gentle and rude VF in the human brain. Based on previous fMRI studies, the selected nodes for the DCM comprised the posterior superior temporal sulcus (pSTS), the inferior parietal lobule (IPL), the premotor cortex (PM), and the DCI. Bayesian model comparison showed that, during action observation, two streams arose from pSTS: one toward IPL, concerning the action goal, and one toward DCI, concerning the action vitality forms. During action execution, two streams arose from PM: one toward IPL, concerning the action goal and one toward DCI concerning action vitality forms. This last finding opens an interesting question concerning the possibility to elicit VF in two distinct ways: cognitively (from PM to DCI) and affectively (from DCI to PM).

Evaluation of potential alterations related to ADHD in the effective connectivity between the default mode network and cerebellum, hippocampus, thalamus, and primary visual cortex.

Hyperactivity in children with attention-deficit/hyperactivity disorder (ADHD) leads to restlessness and impulse-control impairments. Nevertheless, the relation between ADHD symptoms and brain regions interactions remains unclear. We focused on dynamic causal modeling to study the effective connectivity in a fully connected network comprised of four regions of the default mode network (DMN) (linked to response control behaviors) and four other regions with previously-reported structural alterations due to ADHD. Then, via the parametric empirical Bayes analysis, the most significant connections, with the highest correlation to the covariates ADHD/control, age, and sex were extracted. Our results demonstrated a positive correlation between ADHD and effective connectivity between the right cerebellum and three DMN nodes (intrinsically inhibitory connections). Therefore, an increase in the effective connectivity leads to more inhibition imposition from the right cerebellum to DMN that reduces this network activation. The lower DMN activity makes leaving the resting-state easier, which may be involved in the restlessness symptom. Furthermore, our results indicated a negative correlation between age and these connections. We showed that the difference between the average of effective connectivities of ADHD and control groups in the age-range of 7-11 years disappeared after 14 years-old. Therefore, aging tends to alleviate ADHD-specific symptoms.

Human cerebellum and corticocerebellar connections involved in emotional memory enhancement.

Emotional information is better remembered than neutral information. Extensive evidence indicates that the amygdala and its interactions with other cerebral regions play an important role in the memory-enhancing effect of emotional arousal. While the cerebellum has been found to be involved in fear conditioning, its role in emotional enhancement of episodic memory is less clear. To address this issue, we used a whole-brain functional MRI approach in 1,418 healthy participants. First, we identified clusters significantly activated during enhanced memory encoding of negative and positive emotional pictures. In addition to the well-known emotional memory-related cerebral regions, we identified a cluster in the cerebellum. We then used dynamic causal modeling and identified several cerebellar connections with increased connection strength corresponding to enhanced emotional memory, including one to a cluster covering the amygdala and hippocampus, and bidirectional connections with a cluster covering the anterior cingulate cortex. The present findings indicate that the cerebellum is an integral part of a network involved in emotional enhancement of episodic memory.

Altered Neurovascular Coupling for Multidisciplinary Intensive Rehabilitation in Parkinson's Disease.

Effective rehabilitation in Parkinson's disease (PD) is related to brain reorganization with restoration of cortico-subcortical networks and compensation of frontoparietal networks; however, further neural rehabilitation evidence from a multidimensional perspective is needed. To investigate how multidisciplinary intensive rehabilitation treatment affects neurovascular coupling, 31 PD patients (20 female) before and after treatment and 30 healthy controls (17 female) underwent blood oxygenation level-dependent functional magnetic resonance imaging and arterial spin labeling scans. Cerebral blood flow (CBF) was used to measure perfusion, and fractional amplitude of low-frequency fluctuation (fALFF) was used to measure neural activity. The global CBF-fALFF correlation and regional CBF/fALFF ratio were calculated as neurovascular coupling. Dynamic causal modeling (DCM) was used to evaluate treatment-related alterations in the strength and directionality of information flow. Treatment reduced CBF-fALFF correlations. The altered CBF/fALFF exhibited increases in the left angular gyrus and the right inferior parietal gyrus and decreases in the bilateral thalamus and the right superior frontal gyrus. The CBF/fALFF alteration in right superior frontal gyrus showed correlations with motor improvement. Further, DCM indicated increases in connectivity from the superior frontal gyrus and decreases from the thalamus to the inferior parietal gyrus. The benefits of rehabilitation were reflected in the dual mechanism, with restoration of executive control occurring in the initial phase of motor learning and compensation of information integration occurring in the latter phase. These findings may yield multimodal insights into the role of rehabilitation in disease modification and identify the dorsolateral superior frontal gyrus as a potential target for noninvasive neuromodulation in PD.SIGNIFICANCE STATEMENT Although rehabilitation has been proposed as a promising supplemental treatment for PD as it results in brain reorganization, restoring cortico-subcortical networks and eliciting compensatory activation of frontoparietal networks, further multimodal evidence of the neural mechanisms underlying rehabilitation is needed. We measured the ratio of perfusion and neural activity derived from arterial spin labeling and blood oxygenation level-dependent fMRI data and found that benefits of rehabilitation seem to be related to the dual mechanism, restoring executive control in the initial phase of motor learning and compensating for information integration in the latter phase. We also identified the dorsolateral superior frontal gyrus as a potential target for noninvasive neuromodulation in PD patients.

Unraveling how the adolescent brain deals with criticism using dynamic causal modeling.

Sensitivity to criticism, which can be defined as a negative evaluation that a person receives from someone else, is considered a risk factor for the development of psychiatric disorders in adolescents. They may be more vulnerable to social evaluation than adults and exhibit more inadequate emotion regulation strategies such as rumination. The neural network involved in dealing with criticism in adolescents may serve as a biomarker for vulnerability to depression. However, the directions of the functional interactions between the brain regions within this neural network in adolescents are still unclear. In this study, 64 healthy adolescents (aged 14 to 17 years) were asked to listen to a series of self-referential auditory segments, which included negative (critical), positive (praising), and neutral conditions, during fMRI scanning. Dynamic Causal Modeling (DCM) with Parametric Empirical Bayesian (PEB) analysis was performed to map the interactions within the neural network that was engaged during the processing of these segments. Three regions were identified to form the interaction network: the left pregenual anterior cingulate cortex (pgACC), the left dorsolateral prefrontal cortex (DLPFC), and the right precuneus (preCUN). We quantified the modulatory effects of exposure to criticism and praise on the effective connectivity between these brain regions. Being criticized was found to significantly inhibit the effective connectivity from the preCUN to the DLPFC. Adolescents who scored high on the Perceived Criticism Measure (PCM) showed less inhibition of the preCUN-to-DLPFC connectivity when being criticized, which may indicate that they required more engagement of the Central Executive Network (which includes the DLPFC) to sufficiently disengage from negative self-referential processing. Furthermore, the inhibitory connectivity from the DLPFC to the pgACC was strengthened by exposure to praise as well as criticism, suggesting a recruitment of cognitive control over emotional responses when dealing with positive and negative evaluative feedback. Our novel findings contribute to a more profound understanding of how criticism affects the adolescent brain and can help to identify potential biomarkers for vulnerability to develop mood disorders before or during adulthood.

Multimodal acoustic-electric trigeminal nerve stimulation modulates conscious perception.

Multimodal stimulation can reverse pathological neural activity and improve symptoms in neuropsychiatric diseases. Recent research shows that multimodal acoustic-electric trigeminal-nerve stimulation (TNS) (i.e., musical stimulation synchronized to electrical stimulation of the trigeminal nerve) can improve consciousness in patients with disorders of consciousness. However, the reliability and mechanism of this novel approach remain largely unknown. We explored the effects of multimodal acoustic-electric TNS in healthy human participants by assessing conscious perception before and after stimulation using behavioral and neural measures in tactile and auditory target-detection tasks. To explore the mechanisms underlying the putative effects of acoustic-electric stimulation, we fitted a biologically plausible neural network model to the neural data using dynamic causal modeling. We observed that (1) acoustic-electric stimulation improves conscious tactile perception without a concomitant change in auditory perception, (2) this improvement is caused by the interplay of the acoustic and electric stimulation rather than any of the unimodal stimulation alone, and (3) the effect of acoustic-electric stimulation on conscious perception correlates with inter-regional connection changes in a recurrent neural processing model. These results provide evidence that acoustic-electric TNS can promote conscious perception. Alterations in inter-regional cortical connections might be the mechanism by which acoustic-electric TNS achieves its consciousness benefits.

Effect of scanning duration and sample size on reliability in resting state fMRI dynamic causal modeling analysis.

Despite its widespread use, resting-state functional magnetic resonance imaging (rsfMRI) has been criticized for low test-retest reliability. To improve reliability, researchers have recommended using extended scanning durations, increased sample size, and advanced brain connectivity techniques. However, longer scanning runs and larger sample sizes may come with practical challenges and burdens, especially in rare populations. Here we tested if an advanced brain connectivity technique, dynamic causal modeling (DCM), can improve reliability of fMRI effective connectivity (EC) metrics to acceptable levels without extremely long run durations or extremely large samples. Specifically, we employed DCM for EC analysis on rsfMRI data from the Human Connectome Project. To avoid bias, we assessed four distinct DCMs and gradually increased sample sizes in a randomized manner across ten permutations. We employed pseudo true positive and pseudo false positive rates to assess the efficacy of shorter run durations (3.6, 7.2, 10.8, 14.4 min) in replicating the outcomes of the longest scanning duration (28.8 min) when the sample size was fixed at the largest (n = 160 subjects). Similarly, we assessed the efficacy of smaller sample sizes (n = 10, 20, …, 150 subjects) in replicating the outcomes of the largest sample (n = 160 subjects) when the scanning duration was fixed at the longest (28.8 min). Our results revealed that the pseudo false positive rate was below 0.05 for all the analyses. After the scanning duration reached 10.8 min, which yielded a pseudo true positive rate of 92%, further extensions in run time showed no improvements in pseudo true positive rate. Expanding the sample size led to enhanced pseudo true positive rate outcomes, with a plateau at n = 70 subjects for the targeted top one-half of the largest ECs in the reference sample, regardless of whether the longest run duration (28.8 min) or the viable run duration (10.8 min) was employed. Encouragingly, smaller sample sizes exhibited pseudo true positive rates of approximately 80% for n = 20, and 90% for n = 40 subjects. These data suggest that advanced DCM analysis may be a viable option to attain reliable metrics of EC when larger sample sizes or run times are not feasible.

Reduced default mode network effective connectivity in healthy aging is modulated by years of education.

Aging is a major risk factor for neurodegenerative diseases like dementia and Alzheimer's disease. Even in non-pathological aging, decline in cognitive functioning is observed in the majority of the elderly population, necessitating the importance of studying the processes involved in healthy aging in order to identify brain biomarkers that promote the conservation of functioning. The default mode network (DMN) has been of special interest to aging research due to its vulnerability to atrophy and functional decline over the course of aging. Prior work has focused almost exclusively on functional (i.e. undirected) connectivity, yet converging findings are scarce. Therefore, we set out to use spectral dynamic causal modeling to investigate changes in the effective (i.e. directed) connectivity within the DMN and to discover changes in information flow in a sample of cognitively normal adults spanning from 48 to 89 years (n = 63). Age was associated to reduced verbal memory performance. Modeling of effective connectivity revealed a pattern of age-related downregulation of posterior DMN regions driven by inhibitory connections from the hippocampus and middle temporal gyrus. Additionally, there was an observed decline in the hippocampus' susceptibility to network inputs with age, effectively disconnecting itself from other regions. The estimated effective connectivity parameters were robust and able to predict the age in out of sample estimates in a leave-one-out cross-validation. Attained education moderated the effects of aging, largely reversing the observed pattern of inhibitory connectivity. Thus, medial prefrontal cortex, hippocampus and posterior DMN regions formed an excitatory cycle of extrinsic connections related to the interaction of age and education. This suggests a compensatory role of years of education in effective connectivity, stressing a possible target for interventions. Our findings suggest a connection to the concept of cognitive reserve, which attributes a protective effect of educational level on cognitive decline in aging (Stern, 2009).

Resting-state effective connectivity is systematically linked to reappraisal success of high- and low-intensity negative emotions.

Emotion regulation is a process by which individuals modulate their emotional responses to cope with different environmental demands, for example, by reappraising the emotional situation. Here, we tested whether effective connectivity of a reappraisal-related neural network at rest is predictive of successfully regulating high- and low-intensity negative emotions in an emotion-regulation task. Task-based and resting-state functional magnetic resonance imaging (rs-fMRI) data of 28 participants were collected using ultra-high magnetic field strength at 7 Tesla during three scanning sessions. We used spectral dynamic causal modeling (spDCM) on the rs-fMRI data within brain regions modulated by emotion intensity. We found common connectivity patterns for both high- and low-intensity stimuli. Distinctive effective connectivity patterns in relation to low-intensity stimuli were found from frontal regions connecting to temporal regions. Reappraisal success for high-intensity stimuli was predicted by additional connections within the vlPFC and from temporal to frontal regions. Connectivity patterns at rest predicting reappraisal success were generally more pronounced for low-intensity stimuli, suggesting a greater role of stereotyped patterns, potentially reflecting preparedness, when reappraisal was relatively easy to implement. The opposite was true for high-intensity stimuli, which might require a more flexible recruitment of resources beyond what is reflected in resting state connectivity patterns. Resting-state effective connectivity emerged as a robust predictor for successful reappraisal, revealing both shared and distinct network dynamics for high- and low-intensity stimuli. These patterns signify specific preparatory states associated with heightened vigilance, attention, self-awareness, and goal-directed cognitive processing, particularly during reappraisal for mitigating the emotional impact of external stimuli. Our findings hold potential implications for understanding psychopathological alterations in brain connectivity related to affective disorders.

Clinical, behavioral, and electrophysiological profiles along a continuum of suicide risk: evidence from an implicit association task.

BACKGROUND: An urgent need exists to identify neural correlates associated with differing levels of suicide risk and develop novel, rapid-acting therapeutics to modulate activity within these neural networks. METHODS: Electrophysiological correlates of suicide were evaluated using magnetoencephalography (MEG) in 75 adults with differing levels of suicide risk. During MEG scanning, participants completed a modified Life-Death Implicit Association Task. MEG data were source-localized in the gamma (30-58 Hz) frequency, a proxy measure of excitation-inhibition balance. Dynamic causal modeling was used to evaluate differences in connectivity estimates between risk groups. A proof-of-concept, open-label, pilot study of five high risk participants examined changes in gamma power after administration of ketamine (0.5 mg/kg), an NMDAR antagonist with rapid anti-suicide ideation effects. RESULTS: Implicit self-associations with death were stronger in the highest suicide risk group relative to all other groups, which did not differ from each other. Higher gamma power for self-death compared to self-life associations was found in the orbitofrontal cortex for the highest risk group and the insula and posterior cingulate cortex for the lowest risk group. Connectivity estimates between these regions differentiated the highest risk group from the full sample. Implicit associations with death were not affected by ketamine, but enhanced gamma power was found for self-death associations in the left insula post-ketamine compared to baseline. CONCLUSIONS: Differential implicit cognitive processing of life and death appears to be linked to suicide risk, highlighting the need for objective measures of suicidal states. Pharmacotherapies that modulate gamma activity, particularly in the insula, may help mitigate risk.Clinicaltrials.gov identifier: NCT02543983, NCT00397111.

Role of the amygdala in disrupted integration and effective connectivity of cortico-subcortical networks in apathy.

BACKGROUND: Apathy is a quantitative reduction in motivation and goal-directed behaviors, not only observed in neuropsychiatric disorders, but also present in healthy populations. Although brain abnormalities associated with apathy in clinical disorders have been studied, the organization of brain networks in healthy individuals has yet to be identified. METHOD: We examined properties of intrinsic brain networks in healthy individuals with varied levels of apathy. By using functional magnetic resonance imaging in combination with graph theory analysis and dynamic causal modeling analysis, we tested communications among nodes and modules as well as effective connectivity among brain networks. RESULTS: We found that the average participation coefficient of the subcortical network, especially the amygdala, was lower in individuals with high than low apathy. Importantly, we observed weaker effective connectivity fromthe hippocampus and parahippocampal gyrus to the amygdala, and from the amygdala to the parahippocampal gyrus and medial frontal cortex in individuals with apathy. CONCLUSION: These findings suggest that individuals with high apathy exhibit aberrant communication within the cortical-to-subcortical network, characterized by differences in amygdala-related effective connectivity. Our work sheds light on the neural basis of apathy in subclinical populations and may have implications for understanding the development of clinical conditions that feature apathy.

Effector-selective modulation of the effective connectivity within frontoparietal circuits during visuomotor tasks.

Despite extensive research, the functional architecture of the subregions of the dorsal posterior parietal cortex (PPC) involved in sensorimotor processing is far from clear. Here, we draw a thorough picture of the large-scale functional organization of the PPC to disentangle the fronto-parietal networks mediating visuomotor functions. To this aim, we reanalyzed available human functional magnetic resonance imaging data collected during the execution of saccades, hand, and foot pointing, and we combined individual surface-based activation, resting-state functional connectivity, and effective connectivity analyses. We described a functional distinction between a more lateral region in the posterior intraparietal sulcus (lpIPS), preferring saccades over pointing and coupled with the frontal eye fields (FEF) at rest, and a more medial portion (mpIPS) intrinsically correlated to the dorsal premotor cortex (PMd). Dynamic causal modeling revealed feedforward-feedback loops linking lpIPS with FEF during saccades and mpIPS with PMd during pointing, with substantial differences between hand and foot. Despite an intrinsic specialization of the action-specific fronto-parietal networks, our study reveals that their functioning is finely regulated according to the effector to be used, being the dynamic interactions within those networks differently modulated when carrying out a similar movement (i.e. pointing) but with distinct effectors (i.e. hand and foot).

Role of right temporoparietal junction for counterfactual evaluation of partner's decision in ultimatum game.

Humans assess the distributions of resources based on their aversion to unfairness. If a partner distributes in an unfair manner even though the partner had a less unfair distribution option, a recipient will believe that the partner should have chosen the counterfactual option. In this study, we investigated the neural basis for fairness evaluation of actual and counterfactual options in the ultimatum game. In this task, a partner chose one distribution option out of two options, and a participant accepted or rejected the option. The behavioral results showed that the acceptance rate was influenced by counterfactual evaluation (CE), among others, as defined by the difference of monetary amount between the actual and counterfactual options. The functional magnetic resonance imaging results showed that CE was associated with the right ventral angular gyrus (vAG) that provided one of convergent inputs to the supramarginal gyrus related to decision utility, which reflects gross preferences for the distribution options. Furthermore, inhibitory repetitive transcranial magnetic stimulation administered to the right vAG reduced the behavioral component associated with CE. These results suggest that our acceptance/rejection of distribution options relies on multiple processes (monetary amount, disadvantageous inequity, and CE) and that the right vAG causally contributes to CE.

Intrinsic excitability of human right parietal cortex shapes the experienced visual size illusions.

Converging evidence has found that the perceived visual size illusions are heritable, raising the possibility that visual size illusions might be predicted by intrinsic brain activity without external stimuli. Here we measured resting-state brain activity and 2 classic visual size illusions (i.e. the Ebbinghaus and the Ponzo illusions) in succession, and conducted spectral dynamic causal modeling analysis among relevant cortical regions. Results revealed that forward connection from right V1 to superior parietal lobule (SPL) was predictive of the Ebbinghaus illusion, and self-connection in the right SPL predicted the Ponzo illusion. Moreover, disruption of intrinsic activity in the right SPL by repetitive transcranial magnetic stimulation (TMS) temporally increased the Ebbinghaus rather than the Ponzo illusion. These findings provide a better mechanistic understanding of visual size illusions by showing the causal and distinct contributions of right parietal cortex to them, and suggest that spontaneous fluctuations in intrinsic brain activity are relevant to individual difference in behavior.

Dynamic causal modeling of cerebello-cerebral connectivity when sequencing trait-implying actions.

Prior studies suggest that the cerebellum contributes to the prediction of action sequences as well as the detection of social violations. In this dynamic causal modeling study, we explored the effective connectivity of the cerebellum with the cerebrum in processing social action sequences. A first model aimed to explore functional cerebello-cerebral connectivity when learning trait/stereotype-implying action sequences. We found many significant bidirectional connectivities between mentalizing areas of the cerebellum and the cerebrum including the temporo-parietal junction (TPJ) and medial prefrontal cortex (mPFC). Within the cerebrum, we found significant connectivity between the right TPJ and the mPFC, and between the TPJ bilaterally. A second model aimed to investigate cerebello-cerebral connectivity when conflicting information arises. We found many significant closed loops between the cerebellum and cerebral mentalizing (e.g. dorsal mPFC) and executive control areas (e.g. medial and lateral prefrontal cortices). Additional closed loops were found within the cerebral mentalizing and executive networks. The current results confirm prior research on effective connectivity linking the cerebellum with mentalizing areas in the cerebrum for predicting social sequences, and extend it to cerebral executive areas for social violations. Overall, this study emphasizes the critical role of cerebello-cerebral connectivity in understanding social sequences.

Selective modulation of interhemispheric connectivity by transcranial alternating current stimulation influences binaural integration.

Brain connectivity plays a major role in the encoding, transfer, and integration of sensory information. Interregional synchronization of neural oscillations in the γ-frequency band has been suggested as a key mechanism underlying perceptual integration. In a recent study, we found evidence for this hypothesis showing that the modulation of interhemispheric oscillatory synchrony by means of bihemispheric high-density transcranial alternating current stimulation (HD-TACS) affects binaural integration of dichotic acoustic features. Here, we aimed to establish a direct link between oscillatory synchrony, effective brain connectivity, and binaural integration. We experimentally manipulated oscillatory synchrony (using bihemispheric γ-TACS with different interhemispheric phase lags) and assessed the effect on effective brain connectivity and binaural integration (as measured with functional MRI and a dichotic listening task, respectively). We found that TACS reduced intrahemispheric connectivity within the auditory cortices and antiphase (interhemispheric phase lag 180°) TACS modulated connectivity between the two auditory cortices. Importantly, the changes in intra- and interhemispheric connectivity induced by TACS were correlated with changes in perceptual integration. Our results indicate that γ-band synchronization between the two auditory cortices plays a functional role in binaural integration, supporting the proposed role of interregional oscillatory synchrony in perceptual integration.

Delirium is associated with loss of feedback cortical connectivity.

INTRODUCTION: Post-operative delirium (POD) is associated with increased morbidity and mortality but is bereft of treatments, largely due to our limited understanding of the underlying pathophysiology. We hypothesized that delirium reflects a disturbance in cortical connectivity that leads to altered predictions of the sensory environment. METHODS: High-density electroencephalogram recordings during an oddball auditory roving paradigm were collected from 131 patients. Dynamic causal modeling (DCM) analysis facilitated inference about the neuronal connectivity and inhibition-excitation dynamics underlying auditory-evoked responses. RESULTS: Mismatch negativity amplitudes were smaller in patients with POD. DCM showed that delirium was associated with decreased left-sided superior temporal gyrus (l-STG) to auditory cortex feedback connectivity. Feedback connectivity also negatively correlated with delirium severity and systemic inflammation. Increased inhibition of l-STG, with consequent decreases in feed-forward and feed-back connectivity, occurred for oddball tones during delirium. DISCUSSION: Delirium is associated with decreased feedback cortical connectivity, possibly resulting from increased intrinsic inhibitory tone. HIGHLIGHTS: Mismatch negativity amplitude was reduced in patients with delirium. Patients with postoperative delirium had increased feedforward connectivity before surgery. Feedback connectivity was diminished from left-side superior temporal gyrus to left primary auditory sensory area during delirium. Feedback connectivity inversely correlated with inflammation and delirium severity.

Causal Evidence for the Multiple Demand Network in Change Detection: Auditory Mismatch Magnetoencephalography across Focal Neurodegenerative Diseases.

The multiple demand (MD) system is a network of fronto-parietal brain regions active during the organization and control of diverse cognitive operations. It has been argued that this activation may be a nonspecific signal of task difficulty. However, here we provide convergent evidence for a causal role for the MD network in the "simple task" of automatic auditory change detection, through the impairment of top-down control mechanisms. We employ independent structure-function mapping, dynamic causal modeling (DCM), and frequency-resolved functional connectivity analyses of MRI and magnetoencephalography (MEG) from 75 mixed-sex human patients across four neurodegenerative syndromes [behavioral variant fronto-temporal dementia (bvFTD), nonfluent variant primary progressive aphasia (nfvPPA), posterior cortical atrophy (PCA), and Alzheimer's disease mild cognitive impairment with positive amyloid imaging (ADMCI)] and 48 age-matched controls. We show that atrophy of any MD node is sufficient to impair auditory neurophysiological response to change in frequency, location, intensity, continuity, or duration. There was no similar association with atrophy of the cingulo-opercular, salience or language networks, or with global atrophy. MD regions displayed increased functional but decreased effective connectivity as a function of neurodegeneration, suggesting partially effective compensation. Overall, we show that damage to any of the nodes of the MD network is sufficient to impair top-down control of sensation, providing a common mechanism for impaired change detection across dementia syndromes.SIGNIFICANCE STATEMENT Previous evidence for fronto-parietal networks controlling perception is largely associative and may be confounded by task difficulty. Here, we use a preattentive measure of automatic auditory change detection [mismatch negativity (MMN) magnetoencephalography (MEG)] to show that neurodegeneration in any frontal or parietal multiple demand (MD) node impairs primary auditory cortex (A1) neurophysiological response to change through top-down mechanisms. This explains why the impaired ability to respond to change is a core feature across dementias, and other conditions driven by brain network dysfunction, such as schizophrenia. It validates theoretical frameworks in which neurodegenerating networks upregulate connectivity as partially effective compensation. The significance extends beyond network science and dementia, in its construct validation of dynamic causal modeling (DCM), and human confirmation of frequency-resolved analyses of animal neurodegeneration models.

Neurocomputational Underpinnings of Expected Surprise.

Predictive coding accounts of brain functions profoundly influence current approaches to perceptual synthesis. However, a fundamental paradox has emerged, that may be very relevant for understanding hallucinations, psychosis, or cognitive inflexibility: in some situations, surprise or prediction error-related responses can decrease when predicted, and yet, they can increase when we know they are predictable. This paradox is resolved by recognizing that brain responses reflect precision-weighted prediction error. This presses us to disambiguate the contributions of precision and prediction error in electrophysiology. To meet this challenge for the first time, we appeal to a methodology that couples an original experimental paradigm with fine dynamic modeling. We examined brain responses in healthy human participants (N = 20; 10 female) to unexpected and expected surprising sounds, assuming that the latter yield a smaller prediction error but much more amplified by a larger precision weight. Importantly, addressing this modulation requires the modeling of trial-by-trial variations of brain responses, that we reconstructed within a fronto-temporal network by combining EEG and MEG. Our results reveal an adaptive learning of surprise with larger integration of past (relevant) information in the context of expected surprises. Within the auditory hierarchy, this adaptation was found tied down to specific connections and reveals in particular precision encoding through neuronal excitability. Strikingly, these fine processes are automated as sound sequences were unattended. These findings directly speak to applications in psychiatry, where specifically impaired precision weighting has been suggested to be at the heart of several conditions such as schizophrenia and autism.SIGNIFICANCE STATEMENT In perception as Bayesian inference and learning, context sensitivity expresses as the precision weighting of prediction errors. A subtle mechanism that is thought to lie at the heart of several psychiatric conditions. It is thus critical to identify its neurophysiological and computational underpinnings. We revisit the passive auditory oddball paradigm by manipulating sound predictability and use a twofold modeling approach to simultaneous EEG-MEG recordings: (1) trial-by-trial modeling of cortical responses reveals a context-sensitive perceptual learning process; (2) the dynamic causal modeling (DCM) of evoked responses uncovers the associated changes in synaptic efficacy. Predictability discloses a link between precision weighting and self-inhibition of superficial pyramidal (SP) cells, a result that paves the way to a fine description of healthy and pathologic perception.

Arousal modulates the amygdala-insula reciprocal connectivity during naturalistic emotional movie watching.

Emotional arousal is a complex state recruiting distributed cortical and subcortical structures, in which the amygdala and insula play an important role. Although previous neuroimaging studies have showed that the amygdala and insula manifest reciprocal connectivity, the effective connectivities and modulatory patterns on the amygdala-insula interactions underpinning arousal are still largely unknown. One of the reasons may be attributed to static and discrete laboratory brain imaging paradigms used in most existing studies. In this study, by integrating naturalistic-paradigm (i.e., movie watching) functional magnetic resonance imaging (fMRI) with a computational affective model that predicts dynamic arousal for the movie stimuli, we investigated the effective amygdala-insula interactions and the modulatory effect of the input arousal on the effective connections. Specifically, the predicted dynamic arousal of the movie served as regressors in general linear model (GLM) analysis and brain activations were identified accordingly. The regions of interest (i.e., the bilateral amygdala and insula) were localized according to the GLM activation map. The effective connectivity and modulatory effect were then inferred by using dynamic causal modeling (DCM). Our experimental results demonstrated that amygdala was the site of driving arousal input and arousal had a modulatory effect on the reciprocal connections between amygdala and insula. Our study provides novel evidence to the underlying neural mechanisms of arousal in a dynamical naturalistic setting.