Ventromedial Prefrontal Research Articles

Metabotropic Glutamate Receptor 5 as a Potential Biomarker of the Intersection of Trauma and Cannabis Use.

Metabotropic glutamate receptor 5 (mGlu5) dysregulation has been implicated in the pathophysiology of trauma-related psychopathology, and there are direct interactions between the endocannabinoid and glutamatergic systems. However, relationships between cannabis use (CU) and mGlu5 have not been directly investigated in trauma-related psychopathology. Using positron emission tomography with [18F]FPEB, we examined relationships between CU status and mGlu5 availability in vivo in a cross-diagnostic sample of individuals with trauma-related psychopathology (n = 55). Specifically, we tested whether mGlu5 availability in frontolimbic regions of interest (ROIs; dorsolateral prefrontal cortex, orbitofrontal cortex, ventromedial prefrontal cortex, amygdala, hippocampus) differed as a function of CU status. Past-year CU (n = 22) was associated with 18.62%-19.12% higher mGlu5 availability in frontal and 14.24%-16.55% higher mGlu5 in limbic ROIs relative to participants with no recent CU. Similarly, past-month or monthly CU (n = 16) was associated with higher mGlu5 availability in frontal (18.05%-20.62%) and limbic (15.53%-16.83%) ROIs. mGlu5 availability in the orbitofrontal cortex and amygdala was negatively associated with depressive symptoms in the past-year CU group. In both CU groups, exploratory analyses showed negative correlations between mGlu5 availability and sadness across all ROIs and with perceptions of worthlessness and past failures (r's = -.47 to .66, P's = .006-.033) in the ventromedial prefrontal cortex. Participants with CU reported lower mean depressive symptoms (P's = .006-.037) relative to those without CU. These findings have substantial implications for our understanding of interactions between CU and glutamatergic neurotransmission in trauma-related psychopathology, underscoring the need for treatment development efforts to consider the effects of CU in this population.

Cross-species striatal hubs: Linking anatomy to resting-state connectivity

Corticostriatal connections are essential for motivation, cognition, and behavioral flexibility. There is broad interest in using resting-state functional magnetic resonance imaging (rs-fMRI) to link circuit dysfunction in these connections with neuropsychiatric disorders. In this paper, we used tract-tracing data from non-human primates (NHPs) to assess the likelihood of monosynaptic connections being represented in rs-fMRI data of NHPs and humans. We also demonstrated that existing hub locations in the anatomical data can be identified in the rs-fMRI data from both species. To characterize this in detail, we mapped the complete striatal projection zones from 27 tract-tracer injections located in the orbitofrontal cortex (OFC), dorsal anterior cingulate cortex (dACC), ventromedial prefrontal cortex (vmPFC), ventrolateral PFC (vlPFC), and dorsal PFC (dPFC) of macaque monkeys. Rs-fMRI seeds at the same regions of NHP and homologous regions of human brains showed connectivity maps in the striatum mostly consistent with those observed in the tracer data. We then examined the location of overlap in striatal projection zones. The medial rostral dorsal caudate connected with all five frontocortical regions evaluated in this study in both modalities (tract-tracing and rs-fMRI) and species (NHP and human). Other locations in the caudate also presented an overlap of four frontocortical regions, suggesting the existence of different locations with lower levels of input diversity. Small retrograde tracer injections and rs-fMRI seeds in the striatum confirmed these cortical input patterns. This study sets the ground for future studies evaluating rs-fMRI in clinical samples to measure anatomical corticostriatal circuit dysfunction and identify connectional hubs to provide more specific treatment targets for neurological and psychiatric disorders.

Cortico-hippocampal interactions underlie schema-supported memory encoding in older adults.

Although episodic memory is typically impaired in older adults (OAs) compared to young adults (YAs), this deficit is attenuated when OAs can leverage their rich semantic knowledge, such as their knowledge of schemas. Memory is better for items consistent with pre-existing schemas and this effect is larger in OAs. Neuroimaging studies have associated schema use with the ventromedial prefrontal cortex (vmPFC) and hippocampus (HPC), but most of this research has been limited to YAs. This fMRI study investigated the neural mechanisms underlying how schemas boost episodic memory in OAs. Participants encoded scene-object pairs with varying congruency, and memory for the objects was tested the following day. Congruency with schemas enhanced object memory for YAs and, more substantially, for OAs. FMRI analyses examined how cortical modulation of HPC predicted subsequent memory. Congruency-related vmPFC modulation of left HPC enhanced subsequent memory in both age groups, while congruency-related modulation from angular gyrus (AG) boosted subsequent memory only in OAs. Individual differences in cortico-hippocampal modulations indicated that OAs preferentially used their semantic knowledge to facilitate encoding via an AG-HPC interaction, suggesting a compensatory mechanism. Collectively, our findings illustrate age-related differences in how schemas influence episodic memory encoding via distinct routes of cortico-hippocampal interactions.

Neural processing of audiovisual and painful analogue trauma and its relationship with subsequent audiovisual and pain intrusions

ABSTRACT Background: Posttraumatic stress disorder and medically unexplained pain frequently co-occur. While pain is common during traumatic events, the processing of pain during trauma and its relation to audiovisual and pain intrusions is poorly understood. Objective: Here we investigate neural activations during painful analogue trauma, focusing on areas that have been related to threat and pain processing, and how they predict intrusion formation. We also examine the moderating role of cumulative lifetime adversity. Methods: Sixty-five healthy women were assessed using functional magnetic resonance imaging. An analogue trauma was induced by an adaptation of the trauma-film paradigm extended by painful electrical stimulation in a 2 (film: aversive, neutral) x 2 (pain: pain, no-pain) design, followed by 7-day audiovisual and pain intrusion assessment using event-based ecological momentary assessment. Intrusions were fitted with Bayesian multilevel regression and a hurdle lognormal distribution. Results: Conjunction analysis confirmed a wide network including anterior insula (AI) and dorsal anterior cingulate cortex (dACC) being active both, during aversive films and pain. Pain resulted in activation in areas amongst posterior insula and deactivation in a network around ventromedial prefrontal cortex (VMPFC). Higher AI and dACC activity during aversive>neutral film predicted greater audiovisual intrusion probability over time and predicted greater audiovisual intrusion frequency particularly for participants with high lifetime adversity. Lower AI, dACC, hippocampus, and VMPFC activity during pain>no-pain predicted greater pain intrusion probability particularly for participants with high lifetime adversity. Weak regulatory VMPFC activation was associated with both increased audiovisual and pain intrusion frequency. Conclusions: Enhanced AI and dACC processing during aversive films, poor pain vs. no-pain discrimination in AI and dACC, as well as weak regulatory VMPFC processing may be driving factors for intrusion formation, particularly in combination with high lifetime adversity. Results shed light on a potential path for the etiology of PTSD and medically unexplained pain.

Circadian Rhythms in Conditioned Threat Extinction Reflect Time-of-Day Differences in Ventromedial Prefrontal Cortex Neural Processing.

Circadian rhythms in conditioned threat extinction emerge from a tissue-level circadian timekeeper, or local clock, in the ventromedial prefrontal cortex (vmPFC). Yet it remains unclear how this local clock contributes to extinction-dependent adaptations. Here we used single-unit and local field potential analyses to interrogate neural activity in the male rat vmPFC during repeated extinction sessions at different times of day. In association with superior recall of a remote extinction memory during the circadian active phase, vmPFC putative principal neurons exhibited phasic firing that was amplified for cue presentations and diminished at transitions in freezing behavior. Coupling of vmPFC gamma amplitude to the phase of low-frequency oscillations was greater during freezing than mobility, and this difference was augmented during the active phase, highlighting a time-of-day dependence in the organization of freezing- versus mobility-associated cell assemblies. Additionally, a greater proportion of vmPFC neurons were phase-locked to low-frequency oscillations during the active phase, consistent with heightened neural excitability at this time of day. Our results suggest that daily fluctuations in vmPFC excitability precipitate enhanced neural recruitment into extinction-based cell assemblies during the active phase, providing a potential mechanism by which the vmPFC local clock modulates circuit and behavioral plasticity during conditioned threat extinction.

Starting the pill during adolescence: Age of onset and duration of use influence morphology of the hippocampus and ventromedial prefrontal cortex.

From adolescence, women become more likely to experience fear dysregulation. Oral contraceptives (OCs) can modulate the brain regions involved in fear processes. OCs are generally used for years and often initiated during adolescence, a sensitive period where certain brain regions involved in the fear circuitry are still undergoing important reorganization. It remains unknown whether OC use during adolescence may induce long-lasting changes in the fear circuitry. This study aimed to examine whether age of onset moderated the relationship between duration of use and fear-related brain structures. We collected structural MRI data in 98 healthy adult women (61 current users, 37 past users) and extracted grey matter volumes (GMV) and cortical thickness (CT) of key regions of the fear circuitry. Non-linear multiple regressions revealed interaction effects between age of onset and quadratic duration of use on GMV of the right hippocampus and right ventromedial prefrontal cortex (vmPFC). Among women who initiated OCs earlier in adolescence, a short duration of use was associated with smaller hippocampal GMV and thicker vmPFC compared to a longer duration of use. For both GMV and CT of the right vmPFC, women with an early OC onset had more grey matter at a short duration of use than those with a later onset. Our results suggest that OC use earlier in adolescence may induce lasting effects on structural correlates of fear learning and its regulation. These findings support further investigation into the timing of OC use to better comprehend how OCs could disrupt normal brain development processes.

Functional connectivity of the amygdala in relation to high stress and low mindfulness

BackgroundHigh psychological stress has been associated with several brain functional changes, including functional connectivity (FC) alterations in regions such as the prefrontal cortex and the amygdala. This study explored FC alterations associated with high perceived stress, and also investigated whether these neuroimaging features were correlated with low levels of mindfulness. MethodsThis study included 29 adults (12 males and 17 females; mean age: 27.6 ± 3.2) who complained of moderate or higher perceived stress and 31 adults (17 males and 14 females; mean age: 29.2 ± 7.2) who complained of low-level stress on the questionnaire scale. Seed-based resting-state FC analysis was conducted to compare between high and low stress groups. The dorsolateral prefrontal cortex (DLPFC), the ventromedial prefrontal cortex (VMPFC) and the amygdala were selected as seeds. ResultsHigh stress group showed weaker left amygdala-based FC in the left cerebellum crus II and the left orbitofrontal cortex compared with low stress group. High stress group had weaker FC between the left DLPFC and the left inferior parietal lobule. On the contrary, high stress group had stronger FC between the left VMPFC and the left caudate compared with low stress group. Weaker FC between the amygdala and the cerebellum crus II was correlated with lower level of awareness facet of mindfulness. ConclusionsThose with high perceived stress showed low levels of mindfulness and several FC alterations centered on the prefrontal cortex and amygdala. Our findings also suggest that weak amygdala-based FC alterations associated with high psychological stress are related to low-level awareness facet of mindfulness.

Open-Label Placebo Injection for Chronic Back Pain With Functional Neuroimaging

Chronic back pain (CBP) is a leading cause of disability. Placebo treatments often provide as much pain relief as bona fide treatments, such as steroid injections. Open-label (honestly prescribed) placebos (OLPs) may relieve CBP without deception, but OLP mechanisms remain poorly understood. To investigate the long-term efficacy and neurobiological mechanisms of OLP for CBP. A randomized clinical trial of CBP with longitudinal functional magnetic resonance imaging (MRI) comparing OLP with usual care, with 1-year follow-up, was conducted in a university research setting and a community orthopedic clinic. Participants were individuals aged 21 to 70 years with CBP. The trial was conducted from November 2017 to August 2018, with 1-year follow-up completed by November 2019. Data analysis was performed from April 2020 to May 2024. The primary analysis was conducted on an intention-to-treat sample. Participants randomized to OLP received a 1-time subcutaneous lumbar saline injection presented as placebo accompanied by information about the power of placebo to relieve pain, alongside their ongoing care. Usual care participants continued their ongoing care. The primary outcome was pain intensity (0-10, with 0 indicating no pain and 10 the most intense) at 1 month posttreatment. Secondary outcomes included pain interference, depression, anxiety, anger, and sleep quality. Functional MRI was performed before and after treatment during evoked and spontaneous back pain. A total of 101 adults (52 [51.4%] females; mean [SD] age, 40.4 [15.4] years) with moderate severity CBP (mean [SD], 4.10 [1.25] intensity; duration, 9.7 [8.5] years) were enrolled. Compared with usual care, OLP reduced CBP intensity posttreatment (relative reduction, 0.61; Hedges g = 0.45; 95% CI, -0.89 to 0.04; P = .02). Through 1-year follow-up, pain relief did not persist, although significant benefits were observed for depression, anger, anxiety, and sleep disruption (Hedges g = 0.3-0.5; all P < .03). Brain responses to evoked back pain for OLP vs usual care increased in rostral anterior cingulate and ventromedial prefrontal cortex and decreased in somatomotor cortices and thalamus. During spontaneous pain, functional connectivity analyses identified OLP vs usual care increases in ventromedial prefrontal cortex connectivity to the rostral ventral medulla, a pain-modulatory brainstem nucleus. No adverse effects of treatment were reported by participants. In this randomized clinical trial of OLP vs usual care, a single nondeceptive placebo injection reduced CBP intensity for 1 month posttreatment and provided benefits lasting for at least 1 year posttreatment. Brain mechanisms of OLP in a clinical population overlap with those of deceptive placebos in healthy volunteers, including engagement of prefrontal-brainstem pain modulatory pathways. ClinicalTrials.gov Identifier: NCT03294148.

Lower entorhinal cortex thickness is associated with greater financial exploitation vulnerability in cognitively unimpaired older adults.

Research suggests that increased financial exploitation vulnerability due to declining decision making may be an early behavioral manifestation of brain changes occurring in preclinical Alzheimer's disease. One of the earliest documented brain changes during the preclinical phase is neurodegeneration in the entorhinal cortex. The objective of the current study was to examine the association between a measure of financial exploitation vulnerability and thickness in the entorhinal cortex in 97 cognitively unimpaired older adults. We also investigated financial exploitation vulnerability associations with frontal regions typically associated with decision making (e.g. dorsolateral and ventromedial prefrontal cortices), and additionally examined the interactive effect of age and cortical thickness on financial exploitation vulnerability. Results showed that greater financial exploitation vulnerability was associated with significantly lower entorhinal cortex thickness. There was a significant interaction between age and entorhinal cortex thickness on financial exploitation vulnerability, whereby lower entorhinal cortex thickness was associated with greater financial exploitation vulnerability in older participants. When the group was divided by age using a median split (70+ and <70years old), lower entorhinal cortex thickness was associated with greater vulnerability only in the older group. Collectively, these findings suggest that financial exploitation vulnerability may serve as a behavioral manifestation of entorhinal cortex thinning, a phenomenon observed in suboptimal brain aging and preclinical Alzheimer's disease.

Neural response to monetary incentives in acquired adolescent depression after mild traumatic brain injury: Stage 2 Registered Report.

Depression is a common consequence of traumatic brain injury. Separately, spontaneous depression-arising without brain injury-has been linked to abnormal responses in motivational neural circuitry to the anticipation or receipt of rewards. It is unknown if post-injury and spontaneously occurring depression share similar phenotypic profiles. This issue is compounded by the fact that nearly all examinations of these psychiatric sequelae are post hoc: there are rarely any prospective assessments of mood and neural functioning before and after a brain injury. In this Stage 2 Registered Report, we used the Adolescent Brain Cognitive Development Consortium dataset to examine if a disruption in functional neural responses to rewards is present in patients with depression after a mild traumatic brain injury. Notably, this study provides an unparalleled opportunity to examine the trajectory of neuropsychiatric symptoms longitudinally within-subjects. This allowed us to isolate mild traumatic brain injury-specific variance independent from pre-existing functioning. Here, we focus on a case-control comparison between 43 youth who experienced a mild traumatic brain injury between MRI visits, and 43 well-matched controls. Contrary to pre-registered predictions (https://osf.io/h5uba/), there was no statistically credible increase in depression in mild traumatic brain injury cases relative to controls. Mild traumatic brain injury was associated with subtle changes in motivational neural circuit recruitment during the anticipation of incentives on the Monetary Incentive Delay paradigm. Specifically, changes in neural recruitment appeared to reflect a failure to deactivate 'task-negative' brain regions (ventromedial prefrontal cortex), alongside blunted recruitment of 'task-positive' regions (anterior cingulate, anterior insula and caudate), during the anticipation of reward and loss in adolescents following mild brain injuries. Critically, these changes in brain activity were not correlated with depressive symptoms at either visit or depression change scores before and after the brain injury. Increased time since injury was associated with a recovery of cognitive functioning-driven primarily by processing speed differences-but depression did not scale with time since injury. These cognitive changes were also uncorrelated with neural changes after mild traumatic brain injury. This report provides evidence that acquired depression may not be observed as commonly after a mild traumatic brain injury in late childhood and early adolescence, relative to findings in adult cases. Several reasons for these differing findings are considered, including sampling enrichment in retrospective cohort studies, under-reporting of depressive symptoms in parent-report data, and neuroprotective factors in childhood and adolescence.

The ventromedial prefrontal cortex plays an important role in implicit emotion regulation: A focality-optimized multichannel tDCS study in anxiety individuals.

The regulation of emotions is a crucial facet of well-being and social adaptability, with explicit strategies receiving primary attention in prior research. Recent studies, however, emphasize the role of implicit emotion regulation, particularly implicating the ventromedial prefrontal cortex (VMPFC) in association with its implementation. This study delves into the nuanced role of the VMPFC through focality-optimized multichannel transcranial direct current stimulation (tDCS), shedding light on its causal involvement in implicit reappraisal. The primary goal was to evaluate the effectiveness of VMFPC-targeted tDCS and elucidate its role in individuals with high trait anxiety. Participants engaged in implicit and explicit emotion regulation tasks during multichannel tDCS targeting the VMPFC. The outcome measures encompassed negative emotion ratings, pupillary diameter, and saccade count, providing a comprehensive evaluation of emotion regulation efficiency. The intervention exhibited a notable impact, resulting in significant reductions in negative emotion ratings and pupillary reactions during implicit reappraisal, highlighting the indispensable role of the VMPFC in modulating emotional responses. Notably, these effects demonstrated sustained efficacy up to 1 day postintervention. This study underscores the potency of VMPFC-targeted multichannel tDCS in augmenting implicit emotion regulation. This not only contributes insights into the neural mechanisms of emotion regulation but also suggests innovative therapeutic avenues for anxiety disorders. The findings present a promising trajectory for future mood disorder interventions, bridging the gap between implicit emotion regulation and neural stimulation techniques.

Altered Development of the Hurst Exponent in the Medial Prefrontal Cortex in Preschoolers With Autism

BackgroundAtypical balance of excitation (E) and inhibition (I) in the brain is thought to contribute to the emergence and symptomatology of autism spectrum disorder (ASD). E/I ratio can be estimated from resting-state functional magnetic resonance imaging (fMRI) using the Hurst exponent (H). A recent study reported decreased ventromedial prefrontal cortex (vmPFC) H in male adults with ASD. Part of the default mode network (DMN), the vmPFC plays an important role in emotion regulation, decision making, and social cognition. It frequently shows altered function and connectivity in individuals with autism. MethodsThe current study presents the first fMRI evidence of altered early development of vmPFC H and its link to DMN functional connectivity and emotional control in toddlers and preschoolers with ASD. A total of 83 children (45 with ASD), ages 1.5–5 years, underwent natural sleep fMRI as part of a longitudinal study. ResultsIn a cross-sectional analysis, vmPFC H decreased with age in children with ASD, reflecting increasing E/I ratio, but not in typically developing children. This effect remained significant when controlling for gestational age at birth, socioeconomic status, or ethnicity. The same pattern was also observed in a subset of children with longitudinal fMRI data acquired 2 years apart on average. Lower vmPFC H was also associated with reduced functional connectivity within the DMN as well as with higher emotional control deficits (although only significant transdiagnostically). ConclusionsThese results suggest an early onset of E/I imbalances in the vmPFC in ASD, with likely consequences for the maturation of the DMN.

Direct stimulation of anterior insula and ventromedial prefrontal cortex disrupts economic choices

Neural activity within the ventromedial prefrontal cortex (vmPFC) and anterior insula (aIns) is often associated with economic choices and confidence. However, it remains unclear whether these brain regions are causally related to these processes. To address this issue, we leveraged intracranial electrical stimulation (iES) data obtained from patients with epilepsy performing an economic choice task. Our results reveal opposite effects of stimulation on decision-making depending on its location along a dorso-ventral axis within each region. Specifically, stimulation of the ventral subregion within aIns reduces risk-taking by increasing participants’ sensitivity to potential losses, whereas stimulation of the dorsal subregion of aIns and the ventral portion of the vmPFC increases risk-taking by reducing participants’ sensitivity to losses. Moreover, stimulation of the aIns consistently decreases participants’ confidence, regardless of its location within the aIns. These findings suggest the existence of functionally dissociated neural subregions and circuits causally involved in accepting or avoiding challenges.

Age-related neural changes underlying long-term recognition of musical sequences

Aging is often associated with decline in brain processing power and neural predictive capabilities. To challenge this notion, we used magnetoencephalography (MEG) and magnetic resonance imaging (MRI) to record the whole-brain activity of 39 older adults (over 60 years old) and 37 young adults (aged 18–25 years) during recognition of previously memorised and varied musical sequences. Results reveal that when recognising memorised sequences, the brain of older compared to young adults reshapes its functional organisation. In fact, it shows increased early activity in sensory regions such as the left auditory cortex (100 ms and 250 ms after each note), and only moderate decreased activity (350 ms) in medial temporal lobe and prefrontal regions. When processing the varied sequences, older adults show a marked reduction of the fast-scale functionality (250 ms after each note) of higher-order brain regions including hippocampus, ventromedial prefrontal and inferior temporal cortices, while no differences are observed in the auditory cortex. Accordingly, young outperform older adults in the recognition of novel sequences, while no behavioural differences are observed with regards to memorised ones. Our findings show age-related neural changes in predictive and memory processes, integrating existing theories on compensatory neural mechanisms in non-pathological aging.

Bed nucleus of the stria terminalis network responses to unpredictable threat in early alcohol abstinence.

Anxiety during early alcohol abstinence, likely resulting from neural changes caused by chronic alcohol use, contributes to high relapse rates. Studies in rodents show heightened activation during early abstinence in the bed nucleus of the stria terminalis (BNST)-a neural hub for anxiety-and its extended anxiety-related corticolimbic network. Despite the clinical importance of early abstinence, few studies investigate the underlying neural mechanisms. To address this gap, we investigated brain function in early alcohol abstinence (EA = 20, 9 women) relative to controls (HC = 20, 11 women) using an unpredictable threat task shown to engage the BNST and corticolimbic brain regions involved in anxiety and alcohol use disorder (AUD). Group, anxiety, and sex were predictors used to determine whole-brain activation and BNST functional connectivity. We found widespread interactions of group × anxiety and group × anxiety × sex for both activation and BNST connectivity during unpredictable threat. In the EA group, higher anxiety was correlated with activation in the BNST, rostral anterior cingulate cortex (ACC), insula (men only), and dorsal ACC (men only). In the HC group, higher anxiety was negatively correlated with activation in the BNST, nucleus accumbens, thalamus, and insula (men only). For connectivity, anxiety was positively correlated in EA and negatively correlated in HC, between the BNST and the amygdala, ventromedial prefrontal cortex (PFC), and dorsomedial PFC; EA men showed stronger BNST-vmPFC connectivity than HC men. These novel findings provide preliminary evidence for alterations in the BNST and anxiety-related corticolimbic brain regions in early alcohol abstinence, adding to growing literature in humans supporting the BNST's role in anxiety and sex-dependent effects of chronic alcohol use.

Aberrant neural computation of social controllability in nicotine-dependent humans

Social controllability, or the ability to exert control during social interactions, is crucial for optimal decision-making. Inability to do so might contribute to maladaptive behaviors such as smoking, which often takes place in social settings. Here, we examined social controllability in nicotine-dependent humans as they performed an fMRI task where they could influence the offers made by simulated partners. Computational modeling revealed that smokers under-estimated the influence of their actions and self-reported a reduced sense of control, compared to non-smokers. These findings were replicated in a large independent sample of participants recruited online. Neurally, smokers showed reduced tracking of forward projected choice values in the ventromedial prefrontal cortex, and impaired computation of social prediction errors in the midbrain. These results demonstrate that smokers were less accurate in estimating their personal influence when the social environment calls for control, providing a neurocomputational account for the social cognitive deficits in this population. Pre-registrations: OSF Registries|How interoceptive state interacts with value-based decision-making in addiction (fMRI study). OSF Registries|COVID-19: social cognition, mental health, and social distancing (online study).

Probing the neural dynamics of musicians’ and non-musicians’ consonant/dissonant perception: Joint analyses of electrical encephalogram (EEG) and functional magnetic resonance imaging (fMRI)

The perception of two (or more) simultaneous musical notes, depending on their pitch interval(s), could be broadly categorized as consonant or dissonant. Previous literature has suggested that musicians and non-musicians adopt different strategies when discerning music intervals: while musicians rely on the frequency ratios between the two fundamental frequencies, such as “perfect fifth” (3:2) as consonant and “tritone” (45:32) as dissonant intervals; non-musicians may rely on the presence of ‘roughness’ or ‘beats’, generated by the difference of fundamental frequencies, as the key elements of ‘dissonance’. The separate Event-Related Potential (ERP) differences in N1 and P2 along the midline electrodes provided evidence congruent with such ‘separate reliances’. To replicate and to extend, in this study we reran the previous experiment, and separately collected fMRI data of the same protocol (with sparse sampling modifications). The behavioral and EEG results largely corresponded to our previous finding. The fMRI results, with the joint analyses by univariate, psycho-physiological interaction, and representational similarity analysis (RSA) approaches, further reinforce the involvement of central midline-related brain regions, such as ventromedial prefrontal and dorsal anterior cingulate cortex, in consonant/dissonance judgments. The final spatiotemporal searchlight RSA provided convincing evidence that the medial prefrontal cortex, along with the bilateral superior temporal cortex, is the joint locus of midline N1 and dorsal anterior cingulate cortex for the P2 effect (for musicians). Together, these analyses reaffirm that musicians rely more on experience-driven knowledge for consonance/dissonance perception; but also demonstrate the advantages of multiple analyses in constraining the findings from both EEG and fMRI.

Post-treatment alterations in white matter integrity in PTSD: Effects on symptoms and functional connectivity a secondary analysis of an RCT

Post-traumatic stress disorder (PTSD) has been linked to altered communication within the limbic system, including reduced structural connectivity in the uncinate fasciculus (UNC; i.e., decreased fractional anisotropy; FA) and reduced resting-state functional connectivity (RSFC) between the hippocampus and ventromedial prefrontal cortex (vmPFC). Previous research has demonstrated attenuation of PTSD symptoms and alterations in RSFC following exposure-based psychotherapy. However, the relationship between changes in structural and functional connectivity patterns and PTSD symptoms following treatment remains unclear. To investigate this, we conducted a secondary analysis of data from a randomized clinical trial of intensive exposure therapy, evaluating alterations in UNC FA, hippocampus-vmPFC RSFC, and PTSD symptoms before (pre-treatment), 7 days after (post-treatment), and 30 days after (follow-up) the completion of therapy. Our results showed that post-treatment changes in RSFC were positively correlated with post-treatment and follow-up changes in UNC FA and that post-treatment changes in UNC FA were positively correlated with post-treatment and follow-up changes in PTSD symptoms. These findings suggest that early changes in functional connectivity are associated with sustained changes in anatomical connectivity, which in turn are linked to reduced PTSD symptom severity.

Cortico-striatal white-matter connectivity underlies the ability to exert goal-directed control.

The balance between goal-directed and habitual control has been proposed to determine the flexibility of instrumental behaviour, in both humans and animals. This view is supported by neuroscientific studies that have implicated dissociable neural pathways in the ability to flexibly adjust behaviour when outcome values change. A previous Diffusion Tensor Imaging study provided preliminary evidence that flexible instrumental performance depends on the strength of parallel cortico-striatal white-matter pathways previously implicated in goal-directed and habitual control. Specifically, estimated white-matter strength between caudate and ventromedial prefrontal cortex correlated positively with behavioural flexibility, and posterior putamen-premotor cortex connectivity correlated negatively, in line with the notion that these pathways compete for control. However, the sample size of the original study was limited, and so far, there have been no attempts to replicate these findings. In the present study, we aimed to conceptually replicate these findings by testing a large sample of 205 young adults to relate cortico-striatal connectivity to performance on the slips-of-action task. In short, we found only positive neural correlates of goal-directed performance, including striatal connectivity (caudate and anterior putamen) with the dorsolateral prefrontal cortex. However, we failed to provide converging evidence for the existence of a neural habit system that puts limits on the capacity for flexible, goal-directed action. We discuss the implications of our findings for dual-process theories of instrumental action.

Irrational choices via a curvilinear representational geometry for value

We make decisions by comparing values, but it is not yet clear how value is represented in the brain. Many models assume, if only implicitly, that the representational geometry of value is linear. However, in part due to a historical focus on noisy single neurons, rather than neuronal populations, this hypothesis has not been rigorously tested. Here, we examine the representational geometry of value in the ventromedial prefrontal cortex (vmPFC), a part of the brain linked to economic decision-making, in two male rhesus macaques. We find that values are encoded along a curved manifold in vmPFC. This curvilinear geometry predicts a specific pattern of irrational decision-making: that decision-makers will make worse choices when an irrelevant, decoy option is worse in value, compared to when it is better. We observe this type of irrational choices in behavior. Together, these results not only suggest that the representational geometry of value is nonlinear, but that this nonlinearity could impose bounds on rational decision-making.