The current review constitutes the first comprehensive look at the possibility that the mismatch negativity (MMN, the deflection of the auditory ERP/ERF elicited by stimulus change) might be ...generated by so‐called fresh‐afferent neuronal activity. This possibility has been repeatedly ruled out for the past 30 years, with the prevailing theoretical accounts relying on a memory‐based explanation instead. We propose that the MMN is, in essence, a latency‐ and amplitude‐modulated expression of the auditory N1 response, generated by fresh‐afferent activity of cortical neurons that are under nonuniform levels of adaptation.
Lifetime experiences and lifestyle, such as education and engaging in leisure activities, contribute to cognitive reserve (CR), which delays the onset of age-related cognitive decline. Word-finding ...difficulties have been identified as the most prominent cognitive problem in older age. Whether CR mitigates age-related word-finding difficulties is currently unknown. Using picture-naming and verbal fluency tasks, this online study aimed to investigate the effect of CR on word-finding ability in younger, middle-aged, and older adults. All participants were right-handed, monolingual speakers of British English. CR for both the period preceding and coinciding with the COVID-19 pandemic was measured through years of education and questionnaires concerning the frequency of engagement in cognitive, leisure, and physical activities. Linear mixed-effect models demonstrated that older adults were less accurate at action and object naming than middle-aged and younger adults. Higher CR in middle age predicted higher accuracies for action and object naming. Hence, high CR might not only be beneficial in older age, but also in middle age. This benefit will depend on multiple factors: the underlying cognitive processes, individual general cognitive processing abilities, and whether task demands are high. Moreover, younger and middle-aged adults displayed faster object naming compared to older adults. There were no differences between CR scores for the period preceding and coinciding with the pandemic. However, the effect of the COVID-19 pandemic on CR and, subsequently, on word-finding ability might only become apparent in the long term. This article discusses the implications of CR in healthy ageing as well as suggestions for conducting language production studies online.
An unpredictable stimulus elicits a stronger event-related response than a high-probability stimulus. This differential in response magnitude is termed the mismatch negativity (MMN). Over the past ...decade, it has become increasingly popular to explain the MMN terms of predictive coding, a proposed general principle for the way the brain realizes Bayesian inference when it interprets sensory information. This perspective article is a reminder that the issue of MMN generation is far from settled, and that an alternative model in terms of adaptation continues to lurk in the wings. The adaptation model has been discounted because of the unrealistic and simplistic fashion in which it tends to be set up. Here, simulations of auditory cortex incorporating a modern version of the adaptation model are presented. These show that locally operating short-term synaptic depression accounts both for adaptation due to stimulus repetition and for MMN responses. This happens even in cases where adaptation has been ruled out as an explanation of the MMN (e.g., in the stimulus omission paradigm and the multi-standard control paradigm). Simulation models that would demonstrate the viability of predictive coding in a similarly multifaceted way are currently missing from the literature, and the reason for this is discussed in light of the current results.
Abstract
The World Health Organization (WHO) aims to improve our understanding of the factors that promote healthy cognitive aging and combat dementia. Aging theories that consider individual aging ...trajectories are of paramount importance to meet the WHO’s aim. Both the revised Scaffolding Theory of Aging and Cognition (STAC-r) and Cognitive Reserve theory (CR) offer theoretical frameworks for the mechanisms of cognitive aging and the positive influence of an engaged lifestyle. STAC-r additionally considers adverse factors, such as depression. The two theories explain different though partly overlapping aspects of cognitive aging. Currently, it is unclear where the theories agree and differ and what compensation mechanism of age-related cognitive decline might be better explained by either STAC-r, CR, or by both. This review provides an essential discussion of the similarities and differences between these prominent cognitive aging theories, their implications for intervention methods and neurodegenerative disease, and significant shortcomings that have not yet been addressed. This review will direct researchers to common insights in the field and to intervention targets and testable hypotheses for future research. Future research should investigate the potential use of STAC-r in neurodegenerative diseases and provide clarity as to what combination of factors build CR, including their relative importance and when in life they are most effective.
Previous work on the human auditory cortex has revealed areas specialized in spatial processing but how the neurons in these areas represent the location of a sound source remains unknown.
Here, we ...performed a magnetoencephalography (MEG) experiment with the aim of revealing the neural code of auditory space implemented by the human cortex. In a stimulus-specific adaptation paradigm, realistic spatial sound stimuli were presented in pairs of adaptor and probe locations. We found that the attenuation of the N1m response depended strongly on the spatial arrangement of the two sound sources. These location-specific effects showed that sounds originating from locations within the same hemifield activated the same neuronal population regardless of the spatial separation between the sound sources. In contrast, sounds originating from opposite hemifields activated separate groups of neurons.
These results are highly consistent with a rate code of spatial location formed by two opponent populations, one tuned to locations in the left and the other to those in the right. This indicates that the neuronal code of sound source location implemented by the human auditory cortex is similar to that previously found in other primates.
Adaptation, the reduction of neuronal responses by repetitive stimulation, is a ubiquitous feature of auditory cortex (AC). It is not clear what causes adaptation, but short-term synaptic depression ...(STSD) is a potential candidate for the underlying mechanism. In such a case, adaptation can be directly linked with the way AC produces context-sensitive responses such as mismatch negativity and stimulus-specific adaptation observed on the single-unit level. We examined this hypothesis via a computational model based on AC anatomy, which includes serially connected core, belt, and parabelt areas. The model replicates the event-related field (ERF) of the magnetoencephalogram as well as ERF adaptation. The model dynamics are described by excitatory and inhibitory state variables of cell populations, with the excitatory connections modulated by STSD. We analysed the system dynamics by linearising the firing rates and solving the STSD equation using time-scale separation. This allows for characterisation of AC dynamics as a superposition of damped harmonic oscillators, so-called normal modes. We show that repetition suppression of the N1m is due to a mixture of causes, with stimulus repetition modifying both the amplitudes and the frequencies of the normal modes. In this view, adaptation results from a complete reorganisation of AC dynamics rather than a reduction of activity in discrete sources. Further, both the network structure and the balance between excitation and inhibition contribute significantly to the rate with which AC recovers from adaptation. This lifetime of adaptation is longer in the belt and parabelt than in the core area, despite the time constants of STSD being spatially homogeneous. Finally, we critically evaluate the use of a single exponential function to describe recovery from adaptation.
We demonstrate how the structure of auditory cortex can be investigated by combining computational modelling with advanced optimisation methods. We optimise a well-established auditory cortex model ...by means of an evolutionary algorithm. The model describes auditory cortex in terms of multiple core, belt, and parabelt fields. The optimisation process finds the optimum connections between individual fields of auditory cortex so that the model is able to reproduce experimental magnetoencephalographic (MEG) data. In the current study, this data comprised the auditory event-related fields (ERFs) recorded from a human subject in an MEG experiment where the stimulus-onset interval between consecutive tones was varied. The quality of the match between synthesised and experimental waveforms was 98%. The results suggest that neural activity caused by feedback connections plays a particularly important role in shaping ERF morphology. Further, ERFs reflect activity of the entire auditory cortex, and response adaptation due to stimulus repetition emerges from a complete reorganisation of AC dynamics rather than a reduction of activity in discrete sources. Our findings constitute the first stage in establishing a new non-invasive method for uncovering the organisation of the human auditory cortex.
•Structure and connectivity of human AC is studied by combining computational modelling with advanced optimisation methods.•Event-related fields reflect activity of the entire AC and adaptation emerges from a complete reorganisation of AC dynamics.•Neural activity caused by feedback connections seems to play a particularly important role in shaping the ERF morphology.
Efficient speech perception requires the mapping of highly variable acoustic signals to distinct phonetic categories. How the brain overcomes this many-to-one mapping problem has remained unresolved. ...To infer the cortical location, latency, and dependency on attention of categorical speech sound representations in the human brain, we measured stimulus-specific adaptation of neuromagnetic responses to sounds from a phonetic continuum. The participants attended to the sounds while performing a non-phonetic listening task and, in a separate recording condition, ignored the sounds while watching a silent film. Neural adaptation indicative of phoneme category selectivity was found only during the attentive condition in the pars opercularis (POp) of the left inferior frontal gyrus, where the degree of selectivity correlated with the ability of the participants to categorize the phonetic stimuli. Importantly, these category-specific representations were activated at an early latency of 115–140ms, which is compatible with the speed of perceptual phonetic categorization. Further, concurrent functional connectivity was observed between POp and posterior auditory cortical areas. These novel findings suggest that when humans attend to speech, the left POp mediates phonetic categorization through integration of auditory and motor information via the dorsal auditory stream.
•Phoneme category selectivity was found in the left inferior frontal gyrus (LIFG).•The latency was 115–140ms, compatible with the speed of phonetic perception.•The degree of selectivity correlated with behavioral phonetic categorization.•LIFG constrains the interpretation of speech sounds into discrete categories.
Idiopathic Parkinson's disease is characterized by a progressive loss of dopaminergic neurons, but the exact disease aetiology remains largely unknown. To date, Parkinson's disease research has ...mainly focused on nigral dopaminergic neurons, although recent studies suggest disease-related changes also in non-neuronal cells and in midbrain regions beyond the substantia nigra. While there is some evidence for glial involvement in Parkinson's disease, the molecular mechanisms remain poorly understood. The aim of this study was to characterize the contribution of all cell types of the midbrain to Parkinson's disease pathology by single-nuclei RNA sequencing and to assess the cell type-specific risk for Parkinson's disease using the latest genome-wide association study. We profiled >41 000 single-nuclei transcriptomes of post-mortem midbrain from six idiopathic Parkinson's disease patients and five age-/sex-matched controls. To validate our findings in a spatial context, we utilized immunolabelling of the same tissues. Moreover, we analysed Parkinson's disease-associated risk enrichment in genes with cell type-specific expression patterns. We discovered a neuronal cell cluster characterized by CADPS2 overexpression and low TH levels, which was exclusively present in idiopathic Parkinson's disease midbrains. Validation analyses in laser-microdissected neurons suggest that this cluster represents dysfunctional dopaminergic neurons. With regard to glial cells, we observed an increase in nigral microglia in Parkinson's disease patients. Moreover, nigral idiopathic Parkinson's disease microglia were more amoeboid, indicating an activated state. We also discovered a reduction in idiopathic Parkinson's disease oligodendrocyte numbers with the remaining cells being characterized by a stress-induced upregulation of S100B. Parkinson's disease risk variants were associated with glia- and neuron-specific gene expression patterns in idiopathic Parkinson's disease cases. Furthermore, astrocytes and microglia presented idiopathic Parkinson's disease-specific cell proliferation and dysregulation of genes related to unfolded protein response and cytokine signalling. While reactive patient astrocytes showed CD44 overexpression, idiopathic Parkinson's disease microglia revealed a pro-inflammatory trajectory characterized by elevated levels of IL1B, GPNMB and HSP90AA1. Taken together, we generated the first single-nuclei RNA sequencing dataset from the idiopathic Parkinson's disease midbrain, which highlights a disease-specific neuronal cell cluster as well as 'pan-glial' activation as a central mechanism in the pathology of the movement disorder. This finding warrants further research into inflammatory signalling and immunomodulatory treatments in Parkinson's disease.
Incoming sounds are represented in the context of preceding events, and this requires a memory mechanism that integrates information over time. Here, it was demonstrated that response adaptation, the ...suppression of neural responses due to stimulus repetition, might reflect a computational solution that auditory cortex uses for temporal integration. Adaptation is observed in single‐unit measurements as two‐tone forward masking effects and as stimulus‐specific adaptation (SSA). In non‐invasive observations, the amplitude of the auditory N1m response adapts strongly with stimulus repetition, and it is followed by response recovery (the so‐called mismatch response) to rare deviant events. The current computational simulations described the serial core‐belt‐parabelt structure of auditory cortex, and included synaptic adaptation, the short‐term, activity‐dependent depression of excitatory corticocortical connections. It was found that synaptic adaptation is sufficient for columns to respond selectively to tone pairs and complex tone sequences. These responses were defined as combination sensitive, thus reflecting temporal integration, when a strong response to a stimulus sequence was coupled with weaker responses both to the time‐reversed sequence and to the isolated sequence elements. The temporal complexity of the stimulus seemed to be reflected in the proportion of combination‐sensitive columns across the different regions of the model. Our results suggest that while synaptic adaptation produces facilitation and suppression effects, including SSA and the modulation of the N1m response, its functional significance may actually be in its contribution to temporal integration. This integration seems to benefit from the serial structure of auditory cortex.
Using a computational model describing the core‐belt‐parabelt structure of the auditory cortex, we show that short‐term synaptic plasticity leads to temporal integration: combination‐sensitive (CS) responses elicited by tone sequences (panel A in top right figure) but not by reversed or partial versions of the sequence (panels B‐D). In general, slowing down the decay of activity‐dependent synaptic depression (i.e., increasing the adaptation time constant) lead to an increase in CS responses; these became more prevalent in the parabelt as the complexity of stimulation was increased (e.g., from two‐tone to four‐tone sequences). Synaptic plasticity was also found to underlie single‐cell and non‐invasively measured phenomena including stimulus‐specific adaptation, response suppression and facilitation, N1m attenuation, as well as the mismatch negativity.
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