Neurochemical profiles of the anterior temporal lobe predict response of repetitive transcranial magnetic stimulation on semantic processing

The effect of repetitive transcranial magnetic stimulation can vary considerably across individuals, but the reasons for this still remain unclear. Here, we investigated whether the response to continuous theta-burst stimulation (cTBS) – an effective protocol for decreasing cortical excitability – related to individual differences in glutamate and GABA neurotransmission. We applied cTBS over the anterior temporal lobe (ATL), a hub for semantic representation, to explore the relationship between the baseline neurochemical profiles in this region and the response to this stimulation. Our experiments revealed that non-responders (subjects who did not show an inhibitory effect of cTBS on subsequent semantic performance) had higher excitatory-inhibitory balance (glutamate + glutamine/GABA ratio) in the ATL, which led to up-regulated task-induced regional activity as well as increased ATL-connectivity with other semantic regions compared to responders. These results disclose that the baseline neurochemical state of a cortical region can be a significant factor in predicting responses to cTBS.

Evolution of the neurochemical profiles in the G93A-SOD1 mouse model of amyotrophic lateral sclerosis

In vivo 1H magnetic resonance spectroscopy (1H-MRS) investigations of amyotrophic lateral sclerosis (ALS) mouse brain may provide neurochemical profiles and alterations in association with ALS disease progression. We aimed to longitudinally follow neurochemical evolutions of striatum, brainstem and motor cortex of mice transgenic for G93A mutant human superoxide dismutase type-1 (G93A-SOD1), an ALS model. Region-specific neurochemical alterations were detected in asymptomatic G93A-SOD1 mice, particularly in lactate (−19%) and glutamate (+8%) of brainstem, along with γ-amino-butyric acid (−30%), N-acetyl-aspartate (−5%) and ascorbate (+51%) of motor cortex. With disease progression towards the end-stage, increased numbers of metabolic changes of G93A-SOD1 mice were observed (e.g. glutamine levels increased in the brainstem (>+66%) and motor cortex (>+54%)). Through ALS disease progression, an overall increase of glutamine/glutamate in G93A-SOD1 mice was observed in the striatum ( p < 0.01) and even more so in two motor neuron enriched regions, the brainstem and motor cortex ( p < 0.0001). These 1H-MRS data underscore a pattern of neurochemical alterations that are specific to brain regions and to disease stages of the G93A-SOD1 mouse model. These neurochemical changes may contribute to early diagnosis and disease monitoring in ALS patients.

Brexpiprazole: a new leaf on the partial dopamine agonist branch

Objectives: Brexpiprazole is a new dopamine partial agonist antipsychotic in the same class as aripiprazole. This paper will briefly review brexpiprazole and compare it with aripiprazole. Conclusions: Brexpiprazole and aripiprazole are both partial agonists at dopamine D2, and serotonin 5-HT1A and antagonists at serotonin 5-HT2A and noradrenergic α1B receptors. However, the two drugs are significantly different in potencies at various receptors; neurochemical profiles predict that brexpiprazole may be comparable with aripiprazole in its antipsychotic efficacy but may cause less akathisia, extrapyramidal side effects (EPS) and activation. In pivotal trials brexpiprazole demonstrated antipsychotic efficacy in short and long-term studies; it was also found to be an effective adjunct in patients with major depression resistant to antidepressants. Akathisia can occur early in treatment with brexpiprazole, as can minor weight gain and prolactin elevation. Indirect data extrapolations from pivotal studies suggest that brexpiprazole and aripiprazole have comparable efficacy but brexpiprazole may cause less akathisia. Like aripiprazole, brexpiprazole has been approved in the USA for use in schizophrenia and antidepressant-resistant depression. Although much more clinical experience is needed, brexpiprazole appears to be distinct from aripiprazole and a promising new ‘metabolically-friendly’ antipsychotic option for treatment of psychoses and mood disorders.