Systematic Review of the Neural Effect of Electroconvulsive Therapy in Patients with Schizophrenia: Hippocampus and Insula as the Key Regions of Modulation

Objective Electroconvulsive therapy (ECT) has been the most potent treatment option for treatment-resistant schizophrenia (TRS). However, the underlying neural mechanisms of ECT in schizophrenia remain largely unclear. This paper examines studies that investigated structural and functional changes after ECT in patients with schizophrenia. Methods We carried out a systematic review with following terms: ‘ECT’, ‘schizophrenia’, and the terms of various neuroimaging modalities. Results Among the 325 records available from the initial search in May 2020, 17 studies were included. Cerebral blood flow in the frontal, temporal, and striatal structures was shown to be modulated (n=3), although the results were divergent. Magnetic resonance spectroscopy (MRS) studies suggested that the ratio of N-acetyl-aspartate/creatinine was increased in the left prefrontal cortex (PFC; n=2) and left thalamus (n=1). The hippocampus and insula (n=6, respectively) were the most common regions of structural/functional modulation, which also showed symptom associations. Functional connectivity of the default mode network (DMN; n=5), PFC (n=4), and thalamostriatal system (n=2) were also commonly modulated. Conclusion Despite proven effectiveness, there has been a dearth of studies investigating the neurobiological mechanisms underlying ECT. There is preliminary evidence of structural and functional modulation of the hippocampus and insula, functional changes in the DMN, PFC, and thalamostriatal system after ECT in patients with schizophrenia. We discuss the rationale and implications of these findings and the potential mechanism of action of ECT. More studies evaluating the mechanisms of ECT are needed, which could provide a unique window into what leads to treatment response in the otherwise refractory TRS population.

Methylphenidate reduces orienting bias in healthy individuals

Background: Healthy individuals show subtle orienting bias, a phenomenon known as pseudoneglect, reflected in a tendency to direct greater attention toward one hemispace. Accumulating evidence indicates that this bias is an individual trait, and attention is preferentially directed contralaterally to the hemisphere with higher dopamine signaling. Administration of methylphenidate (MPH), a dopamine transporter inhibitor, was shown to normalize aberrant spatial attention bias in psychiatric and neurological patients, suggesting that the reduced orienting bias following administration of MPH reflects an asymmetric effect of the drug, increasing extracellular dopamine in the hemisphere with lower dopamine signaling. Aim: We predicted that, similarly to its effect on patients with brain pathology, MPH will reduce the orienting bias in healthy subjects. Methods: To test this hypothesis, we examined the behavioral effects of a single dose (20 mg) of MPH on orienting bias in 36 healthy subjects (18 females) in a randomized, double-blind placebo-controlled, within-subject design, using the greyscales task, which has been shown to detect subtle attentional biases in both patients and healthy individuals. Results/outcomes: Results demonstrate that healthy individuals vary in both direction and magnitude of spatial orienting bias and show reduced magnitude of orienting bias following MPH administration, regardless of the initial direction of asymmetry. Conclusions/interpretations: Our findings reveal, for the first time in healthy subjects, that MPH decreases spatial orienting bias in an asymmetric manner. Given the well-documented association between orienting bias and asymmetric dopamine signaling, these findings also suggest that MPH might exert a possible asymmetric neural effect in the healthy brain.

Spontaneous mentalizing after early interpersonal trauma: Evidence for hypoactivation of the temporoparietal junction

Experience of interpersonal trauma and violence alters self-other distinction (also known as theory of mind, or ToM), yet little is known about their neural correlates. This fMRI study assessed temporoparietal junction (TPJ) activation, an area strongly implicated in interpersonal processing, during spontaneous mentalizing in 35 adult women with histories of childhood physical, sexual, and/or emotional abuse (childhood abuse; CA) and 31 women without such experiences (unaffected comparisons, UC). Participants watched movies during which an agent formed true or false beliefs about the location of a ball, while participants always knew the true location of the ball. As hypothesized, right TPJ activation was greater for UC compared to CA for false versus true belief conditions. However, posttraumatic stress symptomatology (PTSS) appeared to play a role in driving the neural effect. In addition, CA showed increased functional connectivity relative to UC between the rTPJ and dorsomedial prefrontal cortex. Finally, the agent's false belief about the presence of the ball speeded participants' response (ToM indx), but without group differences. These findings highlight that experiencing early interpersonal trauma can alter brain areas involved in the neural processing of ToM and perspective-taking during adulthood.

148 Using Game Theory in Primates to Study Interactive Social Behavior and its Neural Modulation

INTRODUCTION A cornerstone of social interaction is the ability to anticipate each other's intentions or actions and is critically absent in individuals with disorders such as autism, schizophrenia, antisocial personality and traumatic brain injury. The neuronal basis and causal underpinnings of interactive social behavior, however, remain largely unknown. METHODS A formal framework for studying mutually beneficial decisions in animals is by iterated games such as the iterated prisoner's-dilemma (iPD) game. Here, we trained pairs of Rhesus monkeys to perform an iPD game in which they repeatedly interacted. We then used multi-neuronal recording, stimulation and neuro-chemical modulation to examine the role neural activity in the dorsal anterior cingulate cortex plays in interactive social behavior. RESULTS >We identify a new class of neurons in the primate dorsal anterior cingulate dedicated to predicting the opponent's yet unknown decisions, as well as distinct class of neurons that encoded the monkey's own current decisions independently of the other. Mixed population predictions of the other was remarkably near-optimal compared to behavioral decoders. Direct deep brain stimulation (DBS) of the cingulate selectively biased mutually beneficial interactions between the monkeys but, surprisingly, had no influence on their decisions when no net-positive outcome was possible. Finally, administration of oxytocin markedly increased sociability between the primates and was explained by a selective shift in the self-other encoding properties of the cingulate population. CONCLUSION We discover a specific group of neurons in the primate anterior cingulate that encode social predictions, demonstrate the effect on DBS in the cingulate on interactive social behavior and reveal the neural effect of oxytocin on prosocial behavior.

Effects of Cross-modal Asynchrony on Informational Masking in Human Cortex

In many everyday listening situations, an otherwise audible sound may go unnoticed amid multiple other sounds. This auditory phenomenon, called informational masking (IM), is sensitive to visual input and involves early (50–250 msec) activity in the auditory cortex (the so-called awareness-related negativity). It is still unclear whether and how the timing of visual input influences the neural correlates of IM in auditory cortex. To address this question, we obtained simultaneous behavioral and neural measures of IM from human listeners in the presence of a visual input stream and varied the asynchrony between the visual stream and the rhythmic auditory target stream (in-phase, antiphase, or random). Results show effects of cross-modal asynchrony on both target detectability (RT and sensitivity) and the awareness-related negativity measured with EEG, which were driven primarily by antiphasic audiovisual stimuli. The neural effect was limited to the interval shortly before listeners' behavioral report of the target. Our results indicate that the relative timing of visual input can influence the IM of a target sound in the human auditory cortex. They further show that this audiovisual influence occurs early during the perceptual buildup of the target sound. In summary, these findings provide novel insights into the interaction of IM and multisensory interaction in the human brain.