Task-load-dependent activation of dopaminergic midbrain areas in the absence of reward

Dopamine release in cortical and subcortical structures plays a central role in reward-related neural processes. Within this context, dopaminergic inputs are commonly assumed to play an activating role, facilitating behavioral and cognitive operations necessary to obtain a prospective reward. Here, we provide evidence from human fMRI that this activating role can also be mediated by task-demand-related processes and thus extendsbeyondsituationsthatonlyentailextrinsicmotivatingfactors. Using a visual discrimination task in which varying levels of task demands were precued, we found enhanced hemodynamic activity in the substantia nigra (SN) for high task demands in the absence of reward or similar extrinsic motivating factors. This observation thus indicates that the SN can also be activated in an endogenous fashion. In parallel to its role in reward-related processes, reward-independent activation likely serves to recruit the processing resources needed to meet enhanced task demands. Simultaneously, activity in a wide network of cortical and subcortical control regions was enhanced in response to high task demands, whereas areas of the default-mode network were deactivated more strongly. The present observations suggest that the SN represents a core node within a broader neural network that adjusts the amount of available neural and behavioral resources to changing situational opportunities and task requirements, which is often driven by extrinsic factors but can also be controlled endogenously

Alpha-amylase, cortisol, and pupillary responses to social and non-social dynamic scenes in young children with autism spectrum disorder

The symptoms of Autism Spectrum Disorder (ASD) may manifest from deficits in attention/arousal; previous studies found altered autonomic and attentional responses in ASD. We found a larger tonic pupil size (Anderson & Colombo, 2009) and altered phasic pupillary responses to human faces (Anderson, Colombo, & Shaddy, 2006) in 2-5 year old children with ASD. Children (20 - 72 months of age) with ASD (n = 12), Down syndrome (DS; n = 9), and typical development (TD; n = 11) were presented with a social and a non-social video clip to examine pupil, salivary, and visual scanning measures. The ASD group had (a) a larger tonic pupil size, (b) lower tonic levels of AA, significantly related to tonic pupil size, and (c) increased phasic pupil responses to the social stimulus than controls. These findings provide replication and extension of our previous investigations; underlying pathology and early identification measures in ASD are discussed

Oral implant-prostheses: New teeth for a brighter brain

Several studies have demonstrated that chewing can be regarded as a preventive measure for cognitive impairment, whereas masticatory deficiency, associated with soft-diet feeding, is a risk factor for the development of dementia. At present the link between orofacial sensorimotor activity and cognitive functions is unknown. In subjects with unilateral molar loss we have shown asymmetries in both pupil size and masticatory muscles electromyographic (EMG) activity during clenching: the molar less side was characterized by a lower EMG activity and a smaller pupil. Since implant-prostheses, greatly reduced both the asymmetry in EMG activity and in pupil's size, trigeminal unbalance, leading to unbalance in the activity of the Locus Coeruleus (LC), may be responsible for the pupil's asymmetry. According to the findings obtained in animal models, we propose that the different activity of the right and left LC may induce an asymmetry in brain activity, thus leading to cognitive impairment. According to this hypothesis, prostheses improved the performance in a complex sensorimotor task and increased the mydriasis associated with haptic tasks. In conclusion, the present study indicates that the implant-prosthesis therapy, which reduces the unbalance of trigeminal proprioceptive afferents and the asymmetry in pupil's size, may improve arousal, boosting performance in a complex sensorimotor task

Pupil and Salivary Indicators of Autonomic Dysfunction in Autism Spectrum Disorder

This is the peer reviewed version of the following article: Anderson, C. J., Colombo, J. and Unruh, K. E. (2013), Pupil and salivary indicators of autonomic dysfunction in autism spectrum disorder. Dev. Psychobiol., 55: 465–482. doi:10.1002/dev.21051, which has been published in final form at http://doi.org/10.1002/dev.21051. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.Dysregulated tonic pupil size has been reported in Autism Spectrum Disorder (ASD). Among the possible sources of this dysregulation are disruptions in the feedback loop between norepinephrine (NE) and hypothalamic systems. In the current study, we examined afternoon levels of salivary alpha-amylase (sAA, a putative correlate of NE) and cortisol (used to assess stress-based responses) in two independent samples of children with ASD. We found a larger pupil size and lower sAA levels in ASD, compared to typical and clinical age-matched controls. This was substantiated at the individual level, as sAA levels were strongly correlated with tonic pupil size. Relatively little diurnal variation in sAA taken in the home environment in the ASD group was also observed, while typical controls showed a significant linear increase throughout the day. Results are discussed in terms of potential early biomarkers and the elucidation of underlying neural dysfunction in ASD

Priorities for research on neuromodulatory subcortical systems in Alzheimer's disease: Position paper from the NSS PIA of ISTAART

The neuromodulatory subcortical system (NSS) nuclei are critical hubs for survival, hedonic tone, and homeostasis. Tau-associated NSS degeneration occurs early in Alzheimer's disease (AD) pathogenesis, long before the emergence of pathognomonic memory dysfunction and cortical lesions. Accumulating evidence supports the role of NSS dysfunction and degeneration in the behavioral and neuropsychiatric manifestations featured early in AD. Experimental studies even suggest that AD-associated NSS degeneration drives brain neuroinflammatory status and contributes to disease progression, including the exacerbation of cortical lesions. Given the important pathophysiologic and etiologic roles that involve the NSS in early AD stages, there is an urgent need to expand our understanding of the mechanisms underlying NSS vulnerability and more precisely detail the clinical progression of NSS changes in AD. Here, the NSS Professional Interest Area of the International Society to Advance Alzheimer's Research and Treatment highlights knowledge gaps about NSS within AD and provides recommendations for priorities specific to clinical research, biomarker development, modeling, and intervention. HIGHLIGHTS: Neuromodulatory nuclei degenerate in early Alzheimer's disease pathological stages. Alzheimer's pathophysiology is exacerbated by neuromodulatory nuclei degeneration. Neuromodulatory nuclei degeneration drives neuropsychiatric symptoms in dementia. Biomarkers of neuromodulatory integrity would be value-creating for dementia care. Neuromodulatory nuclei present strategic prospects for disease-modifying therapies

Evidence for a modulating effect of transcutaneous auricular vagus nerve stimulation (taVNS) on salivary alpha-amylase as indirect noradrenergic marker: A pooled mega-analysis.

BACKGROUND Non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) has received tremendous attention as a potential neuromodulator of cognitive and affective functions, which likely exerts its effects via activation of the locus coeruleus-noradrenaline (LC-NA) system. Reliable effects of taVNS on markers of LC-NA system activity, however, have not been demonstrated yet. METHODS The aim of the present study was to overcome previous limitations by pooling raw data from a large sample of ten taVNS studies (371 healthy participants) that collected salivary alpha-amylase (sAA) as a potential marker of central NA release. RESULTS While a meta-analytic approach using summary statistics did not yield any significant effects, linear mixed model analyses showed that afferent stimulation of the vagus nerve via taVNS increased sAA levels compared to sham stimulation (b = 0.16, SE = 0.05, p = 0.001). When considering potential confounders of sAA, we further replicated previous findings on the diurnal trajectory of sAA activity. CONCLUSION(S) Vagal activation via taVNS increases sAA release compared to sham stimulation, which likely substantiates the assumption that taVNS triggers NA release. Moreover, our results highlight the benefits of data pooling and data sharing in order to allow stronger conclusions in research

Pupil dynamics during very light exercise predict benefits to prefrontal cognition

軽運動の前頭前野機能向上効果は瞳に映る. 京都大学プレスリリース. 2023-07-12.Physical exercise, even stress-free very-light-intensity exercise such as yoga and very slow running, can have beneficial effects on executive function, possibly by potentiating prefrontal cortical activity. However, the exact mechanisms underlying this potentiation have not been identified. Evidence from studies using pupillometry demonstrates that pupil changes track the real-time dynamics of activity linked to arousal and attention, including neural circuits from the locus coeruleus to the cortex. This makes it possible to examine whether pupil-linked brain dynamics induced during very-light-intensity exercise mediate benefits to prefrontal executive function in healthy young adults. In this experiment, pupil diameter was measured during 10 min of very-light-intensity exercise (30% V̇o2peak). A Stroop task was used to assess executive function before and after exercise. Prefrontal cortical activation during the task was assessed using multichannel functional near-infrared spectroscopy (fNIRS). We observed that very-light-intensity exercise significantly elicited pupil dilation, reduction of Stroop interference, and task-related left dorsolateral prefrontal cortex activation compared with the resting-control condition. The magnitude of change in pupil dilation predicted the magnitude of improvement in Stroop performance. In addition, causal mediation analysis showed that pupil dilation during very-light-intensity exercise robustly determined subsequent enhancement of Stroop performance. This finding supports our hypothesis that the pupil-linked mechanisms, which may be tied to locus coeruleus activation, are a potential mechanism by which very light exercise enhances prefrontal cortex activation and executive function. It also suggests that pupillometry may be a useful tool to interpret the beneficial impact of exercise on boosting cognition

Body patterning and cognition in cephalopods - a literature review

Cephalopods are a valuable model for studying the evolution of cognition due to their distinctive brain structure, organisation, and connectivity patterns compared to vertebrates. The development of large brains and behavioural complexities are believed to be triggered by evolutionary pressures stemming from factors like heightened predation, more demanding foraging conditions, and intense mating competition. While the differences between corvid and mammals are less pronounced, the cephalopod brain is closer to the vertebrate brain in terms of encephalisation of ganglionic masses observed by nerve cell clusters. The cerebral ganglion in cephalopods is similar to the vertebrate forebrain and midbrain, while the vertical lobe is similar to the vertebrate cerebral cortex and hippocampus formation, which are involved in learning and memory. These brain regions function in a hierarchical system and are intimately connected with their eyes and optic lobes where visual inputs are processed, motor commands are transmitted to the lower motor centre. Chromatophores are skin elements and the physiological control of body patterning and are visually driven and light sensitive. This sets cephalopods apart from their molluscan families such as gastropods and bivalves. Recent studies have revealed that the opsins present in the skin are like those occurring in the retina. This infers that the connection between visual processing and body patterns is not exclusively innate. Expanding on Macphail's Null Hypothesis which posits no significant qualitative or quantitative differences in intelligence across vertebrates, this study seeks to explore the link between body patterning and cognitive abilities across cephalopod species. By comparing patterns of similarities and differences in cognitive abilities, this study aims to investigate whether body patterning can serve as an indicator of cognitive capacity. In conclusion, the study finds the presence of interindividual variations within species and disparities across different species in both body patterning and cognitive abilities. There are associations between cognitive capacity and body patterns. However, establishing a direct and conclusive connection between high-level cognitive abilities and the expression of body patterns remains elusive, as concrete evidence supporting such a relationship is lacking.Cephalopoda utgör en värdefull modell för att studera den kognitiva evolutionen på grund av deras distinkta hjärnstruktur, organisation och nervernas kontaktmönster jämfört med ryggradsdjur. Utvecklingen av stora hjärnor och komplexa beteenden tros vara resultatet av evolutionär press från faktorer som ökad predation, mer krävande födosökningsförhållanden och intensiv parningskonkurrens. Medan skillnaderna mellan kråkfåglar och däggdjur är mindre uttalade, är bläckfiskhjärnan närmare ryggradsdjurshjärnan när det gäller encefalisering av nervcellkluster. Det cerebrala ganglie hos bläckfiskar liknar ryggradsdjurens främre hjärna och mellanhjärna, medan den vertikala loben liknar ryggradsdjurens hjärnbark och hippocampusformation, som är involverade i inlärning och minne. Dessa hjärnregioner fungerar inom ett hierarkiskt system och är intimt kopplade till deras ögon och optiska lober där visuell information bearbetas och motoriska kommandon överförs till de nedre motoriska centrarna. Kromatoforer är hudstrukturer som fysiologiskt kontrollerar kroppsmönster och är visuellt styrda och ljuskänsliga. Detta skiljer cephalopoder från andra molluskfamiljer som gastropoder och musslor. Studier har nyligenavslöjat att de opsin som finns i huden liknar de som förekommer i näthinnan. Detta antyder att sambandet mellan visuell bearbetning och kroppsmönster inte är uteslutande medfödd. Utöver Macphails nollhypotes, som hävdar att det inte finns några signifikanta kvalitativa eller kvantitativa skillnader i intelligens mellan ryggradsdjur, ämnar denna studie utforska kopplingen mellan kroppsmönster och kognitiva förmågor hos cephalopoda. Genom att jämföra likheter och skillnader i kognitiva förmågor syftar denna studie till att undersöka om kroppsmönster kan fungera som en indikator på kognitiv kapacitet. Resultaten visar på förekomst av variationer mellan individer inom arter och skillnader mellan olika arter både vad gäller kroppsmönster och kognitiva förmågor. Det finns samband mellan kognitiv kapacitet och funktioner samt kroppsmönster. Dock är det fortfarande svårt att fastställa en direkt och definitiv koppling mellan hög kognitiva förmågor och uttrycket av kroppsmönster, eftersom konkret bevis som stöder ett sådant samband saknas