Table 1 Summary of key neuroplasticity processes and examples of their disruption in psychosis spectrum illnesses.

Synaptic plasticity

The activity-dependent modification of the efficiency or strength of synaptic transmission at pre-existing synapses

Abnormally elevated microglial synaptic engulfment [138]

Spike-timing dependent plasticity

The process by which synaptic transmission is enhanced or depressed, based on the order and precise temporal interval between presynaptic and postsynaptic spikes; its relative importance varies across synapses and activity regimes

Spike timing activity in PFC is disrupted by NMDAR blockade in a nonhuman primate model of schizophrenia [17]

Critical period (experience-expectant) plasticity

An epoch in brain development where large-scale changes in neuronal response selectivity can be induced by passive exposure to specific forms of environmental inputs; requires that intrinsic maturational programs and environmental inputs are temporally aligned

Alterations in critical period transcriptomics [145].

Hebbian (experience-dependent or activity-dependent) plasticity

A form of synaptic plasticity which is induced by and further amplifies correlations in neuronal activity; outside of the critical period, it is harnessed as a function of alertness, attention, incentive salience of inputs, and behavioral outcome

–Impaired LTP-like responses in visual cortex [191];

–Impaired neurostimulation-induced LTP- and LTD-like effects [169]

Homeostatic plasticity

A set of neuronal changes that restores activity to a setpoint following perturbation; creates balance between intrinsic excitability and synaptic strength, and between network excitation and inhibition; coordinates changes in circuit connectivity

Hypothesized functional and structural and synaptic downregulation that occurs in response to initial microcircuit hyperexcitation [4]

Compensatory plasticity

The capacity to adapt to the loss of neural macrocircuit (or cortical sector) function by undergoing plastic changes in neural interactions, circuit structure, and/or circuit connectivity.

–Thalamic hypoconnectivity between prefrontal-striatal-cerebellar regions and hyperconnectivity with sensory-motor cortices [177]

–Abnormal recruitment of VWFA during auditory working memory in people with psychosis [181]

Synaptic scaling

A negative feedback mechanism to changes in the level of network activity, in which the synaptic strengths of a neuron are modified by regulating synaptic receptors following a scaling factor. The total synaptic input is adjusted to match the neuron’s homeostatic range while preserving the relative differences among synaptic weights

Computational modeling of EEG and fMRI data indicating reduced pyramidal cell synaptic gain [192]

Metaplasticity

Activity-dependent changes in neural functions that modulate subsequent synaptic plasticity responses.

Early childhood adverse experiences increase the risk for schizophrenia [51]