Reduced serial dependence suggests deficits in synaptic potentiation in anti-NMDAR encephalitis and schizophrenia

Stein, Heike; Barbosa, João; Rosa-Justicia, Mireia; Prades, Laia; Morató, Alba; Galan-Gadea, Adrià; Ariño, Helena; Martínez‐Hernández, Eugenia; Castro‐Fornieles, Josefina; Dalmau, Josep; Compte, Albert

doi:10.1038/s41467-020-18033-3

Cited by 56 publications

(76 citation statements)

References 72 publications

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“…To improve power, we ‘folded’ our response data such that, when examining bias at 30° we included values from 22°− 38° as well as responses from −22°− (−38°) by inverting both the responses and probe offsets (δθ) for the negative values of Δθ. This procedure removes any systematic responses biases (e.g., favoring CW responses) and, as a result, the figures presenting serial dependence have rotational symmetry across the origin 34,58 .…”

Section: Methodsmentioning

confidence: 99%

Sensory readout accounts for adaptation

Sheehan¹,

Jt²

2021

Preprint

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Sensory responses and behavior are strongly shaped by stimulus history. For instance, perceptual reports are sometimes biased towards previously viewed stimuli (serial dependence). Previous behavioral studies suggest that serial dependence is implemented via modulations in visual cortex, but neural evidence is lacking. We recorded fMRI responses while human participants performed a delayed orientation discrimination task. While behavioral reports were attracted to the previous stimulus, response patterns in sensory areas were repelled. We reconciled these opposing biases using a model where both sensory encoding and readout are shaped by stimulus history. Neural adaptation reduces redundancy at encoding and leads to the repulsive biases that we observed in visual cortex. Serial dependence is not implemented in visual cortex but rather by readout mechanisms that account for adaptation during encoding. The model suggests the visual system improves efficiency via adaptation while still optimizing behavioral readout based on the temporal structure of natural stimuli.

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Section: Methodsmentioning

confidence: 99%

Sensory readout accounts for adaptation

Sheehan¹,

Jt²

2021

Preprint

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“…Our results show a notable convergence with recent studies in patients with schizophrenia reporting a similarly marked shift in state preference [11] as well as increased overall transition frequencies [34], and altered modular network structure. [30] Given the considerable overlap in psychiatric symptoms in patients with schizophrenia and NMDARE [35,36] and the glutamate hypothesis positing NMDA receptor dysfunction as pathophysiological basis for cognitive and psychiatric symptoms in schizophrenia, [37,38] our findings raise the interesting possibility that the transdiagnostic psychopathological profile of both diseases [39] could be paralleled by a common set of dynamic network alterations. This should be addressed in comparative studies of NMDARE and schizophrenia that use the same MRI acquisition and analysis protocols.…”

Section: Relation To Schizophreniamentioning

confidence: 76%

State-dependent signatures of Anti-NMDA Receptor Encephalitis: a dynamic functional connectivity study

Schwanenflug

Krohn

Heine

et al. 2020

Preprint

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IntroductionAnti-N-methyl-d-aspartate receptor encephalitis (NMDARE) is an autoimmune disorder associated with severe neuropsychiatric symptoms. While patients with NMDARE exhibit disrupted functional connectivity (FC), these findings have been limited to static connectivity analyses. This study applies time-resolved FC analysis to explore the temporal variability of large-scale brain activity in NMDARE and to assess the discriminatory power of functional brain states in a supervised classification approach. MethodsResting-state fMRI data from 57 patients with NMDARE and 61 controls was included. To capture brain dynamics, four discrete connectivity states were extracted and state-wise group differences in FC, occurrence, dwell time and transition frequency were assessed. Furthermore, logistic regression models with embedded feature selection were trained for each state to predict group status in a leave-one-out cross validation scheme. ResultsPatients showed FC alterations in three out of four states. Besides a reduction in hippocampalfrontal connectivity, we observed connectivity decreases within the default mode network and between frontal areas and subcortical as well as visual regions, which remained undetected in static FC. Furthermore, patients displayed a shift in dwell time from the weakly connected dominant state to a higher connected, but less frequent state, accompanied by increased transition frequencies. Discriminatory network features and predictive power varied dynamically over states, reaching up to 78.6% classification accuracy. ConclusionPatients showed state-specific alterations in FC along with a shift in dwell time and increased volatility of state transitions. These measures were associated with disease severity and duration, highlighting the potential of spatiotemporal dynamics in FC as prognostic biomarkers in NMDARE.

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“…given cortical synaptic gain is decreased (e.g. reduced function of NMDA 1,2,5 , dopamine 1 9 and muscarinic 10 receptors), and inhibitory interneurons downregulated 4,7 , then the simplest interpretation of increases and decreases in pyramidal self-inhibition are diminished pyramidal synaptic gain 28,45 and decreased interneuron function, respectively.…”

Section: Discussionmentioning

confidence: 99%

Computational modelling of EEG and fMRI paradigms reveals a consistent loss of pyramidal cell synaptic gain in schizophrenia

Adams

Pinotsis

Tsirlis

et al. 2021

Preprint

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Diminished synaptic gain – the sensitivity of postsynaptic responses to neural inputs – may be a fundamental synaptic pathology in schizophrenia. Evidence for this is indirect, however. Furthermore, it is unclear whether pyramidal cells or interneurons (or both) are affected, or how these deficits relate to symptoms. Participants with schizophrenia (Scz, n=108), their relatives (n=57), and controls (n=107) underwent three electroencephalography paradigms – resting, mismatch negativity, and 40 Hz auditory steady-state response – and resting functional magnetic resonance imaging. Dynamic causal modelling was used to quantify synaptic connectivity in cortical microcircuits. Across all four paradigms, characteristic Scz data features were best explained by models with greater self-inhibition (decreased synaptic gain), in pyramidal cells. Furthermore, disinhibition in auditory areas predicted abnormal auditory perception (and positive symptoms) in Scz, in three paradigms. Thus, psychotic symptoms of Scz may result from a downregulation of inhibitory interneurons that may compensate for diminished postsynaptic gain in pyramidal cells.

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Reduced serial dependence suggests deficits in synaptic potentiation in anti-NMDAR encephalitis and schizophrenia

Cited by 56 publications

References 72 publications

Sensory readout accounts for adaptation

Sensory readout accounts for adaptation

State-dependent signatures of Anti-NMDA Receptor Encephalitis: a dynamic functional connectivity study

Computational modelling of EEG and fMRI paradigms reveals a consistent loss of pyramidal cell synaptic gain in schizophrenia

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