Modulation of brain activity with transcranial direct current stimulation: Targeting regions implicated in impaired illness awareness in schizophrenia

Abstract

Background: Impaired illness awareness or insight into illness (IIA) is a common feature of schizophrenia that contributes to medication nonadherence and poor clinical outcomes. Neuroimaging studies suggest IIA may arise from interhemispheric imbalance in frontoparietal regions, particularly in the posterior parietal area (PPA) and the dorsolateral prefrontal cortex (dlPFC). In this pilot study, we examined the effects of transcranial direct current stimulation (tDCS) on brain regions implicated in IIA. Methods: Eleven patients with schizophrenia with IIA (!3 PANSS G12) and 10 healthy controls were included. A crossover design was employed where all participants received single-session bi-frontal, biparietal, and sham stimulation in random order. For each condition, we measured (i) blood oxygen leveldependent (BOLD) response to an illness awareness task pre-and post-stimulation, (ii) regional cerebral blood-flow (rCBF) prior to and during stimulation, and (iii) changes in illness awareness. Results: At baseline, patients with schizophrenia showed higher BOLD-response to an illness awareness task in the left-PPA compared to healthy controls. Bi-parietal stimulation reduced the interhemispheric imbalance in the PPA compared to sham stimulation. Relatedly, bi-parietal stimulation increased rCBF beneath the anode (21% increase in the right-PPA), but not beneath the cathode (5.6% increase in the left-PPA). Bi-frontal stimulation did not induce changes in rCBF. We found no changes in illness awareness. Conclusion: Although single-session tDCS did not improve illness awareness, this pilot study provides mechanistic justification for future investigations to determine if multi-session bi-parietal tDCS can induce sustained changes in brain activity in the PPA in association with improved illness awareness.

Improvement of Insight with Non-Invasive Brain Stimulation in Patients with Schizophrenia: A Systematic Review

“…We selected six RCTs [ 39 , 40 , 41 , 42 , 43 , 44 ], three open-label studies [ 45 , 46 , 47 ], one case series [ 48 ] and four case reports [ 49 , 50 , 51 , 52 ]. The studies came from five independent research groups.…”

“…In total, the included studies recruited 226 patients, with mean age ranging from 24 to 46.4 and a sex-ratio of 1.073 (117 males and 109 females). Almost all the patients were right-handed: Nine studies included exclusively right-handed patients [ 40 , 41 , 43 , 44 , 45 , 48 , 50 , 51 , 52 ]; two studies reported to have included mixed samples with non-right-handed patients [ 39 , 47 ]; three studies did not provide information regarding handedness; and Kim et al (2019) reported a mean score of 77.6 ± 16.2 at the Edinburgh Handedness Inventory [ 53 ]. Most of the patients included were on antipsychotic medication but two case-reports included drug-free patients [ 50 , 51 ].…”

“…Most of the patients included were on antipsychotic medication but two case-reports included drug-free patients [ 50 , 51 ]. The six RCTs included a mixed sample of patients with schizophrenia and schizoaffective disorders [ 39 , 40 , 41 , 42 , 43 , 44 ]. The other articles exclusively included patients with schizophrenia.…”

“…Almost half of the studies included patients with treatment-resistant auditory hallucinations (6 out of 14) [ 40 , 41 , 43 , 45 , 46 , 47 ] or negative symptoms (3 out of 14) [ 39 , 42 , 48 ]. One study specifically included patients with impaired illness awareness [ 44 ]. The four remaining case reports included difficult-to-treat patients.…”

“…Overall, clinical insight was the most studied dimension of insight. Six different clinician-rated and self-rated scales were used to measure clinical insight: the Scale for Assessment of Unawareness of Mental Disorder (SUMD) was used by three studies [ 48 , 49 , 50 ] in its original version [ 54 ] and by two studies [ 39 , 41 ] in its abbreviated version [ 55 ], the Birchwood Insight Scale (BIS, [ 56 ]) was used by three studies [ 42 , 51 , 52 ], the Schedule for Assessment of Insight (SAI [ 10 ]) was used by two studies [ 45 , 46 ], the Self-Appraisal of Illness Questionnaire (SAIQ [ 57 ]) by two studies [ 39 , 43 ] and the VAGUS insight into psychosis scale was used by two studies [ 44 , 47 ], either with the version rated by the clinician (VAGUS-CR: clinician-rated) or the one rated by the patient (VAGUS-SR: self-reported) [ 58 ]. Finally, two studies [ 40 , 43 ] used the G12 “lack of judgement and insight” single-item score of the positive and negative syndrome scale (PANSS) [ 59 ] (range 1–7 with higher score representing lower insight) to provide a measure of clinical insight, associated with another scale measuring clinical or cognitive insight.…”