2019 Research Forum

Multiple Neuroimaging Modalities Consistently Implicating Location of Auditory Verbal Hallucinations (AVH) in Patients with Schizophrenia to the Left Temporal Gyri

Surag Gohel, MD R3, MPH, Arezou Babaesfahani MS IV, Peter De Mola MS IV, Mohammed Molla, MD, DFAPA UCLA-Kern Psychiatry Residency Training Program

Introduction

Discussion

Introduction

Auditory verbal hallucinations (AVHs) are the phenomenon of hearing voices in absence of speaker, and are experienced by 60-80% of people with schizophrenia. Researchers have long sought to identify the region of the brain responsible for the generation of AVH in order to develop more targeted treatments. Given the advancement of neuroimaging and its increased availability since 1985, multiple neuroimaging studies have been performed utilizing various modalities in patients with schizophrenia. With the abundance of this new data, this study aims to identify the brain region responsible for auditory verbal hallucinations via a literature review of 30 publications employing various neuroimaging modalities including:

To date, schizophrenia with prominent AVH remains principally a clinical diagnosis. Our thorough review of 30 publications revealed that multiple neuroimaging modalities can objectively identify distinct changes in the anatomical structure, activity and connectivity within the left temporal lobe which appears as an epicenter of AVH origin. A deeper understanding of neuroimaging abnormalities which precipitate AVH has the potential to offer new avenues of psychiatric treatments, particularly with transcranial magnetic stimulation (TMS) , tDCS and deep brain stimulation (DBS). Literature review also demonstrated defective left STG attenuation during inner speech monitoring which can potentially be modulated with cognitive behavioral therapy (CBT). Patients could be trained to be more cognizant of inner speech rather than misattributing the voices as not their own. Leveraging real-time neurofeedback using fMRI could also be used to self-modulate activity in hyperactive regions such as the left STG. Continuing research in alternative treatment options is imperative given a large portion of patients remain refractory to antipsychotic drugs. Determining which pathways demonstrate abnormal connectivity in relation to AVH provides psychiatrists the foundation to implement tDCS to reduce AVH intensity and frequency. Implementation of tDCS between the left temporal lobe and other implicated regions of the brain has shown great promise. There is also the potential to go further with DBS+ electrodes to apply more precise treatment to key problematic region. These findings are not limited to developing novel treatments, but can also be applied toward screening individuals at high risk for developing AVH-prone schizophrenia. MRI studies measuring left temporal cortical thickness in AVH-prone patients also examined their unaffected first degree relatives and intriguingly observed an intermediate result between affected patients and healthy controls. 1. Cui, Y., Liu, B., Song, M., Lipnicki, D. M., Li, J., Xie, S., . . . Jiang, T. (2017). Auditory verbal hallucinations are related to cortical thinning in the left middle temporal gyrus of patients with schizophrenia. Psychological Medicine, 48(01), 115-122. doi:10.1017/s0033291717001520 2. Shergill, S. S., Tracy, D. K., Sanghera, K., Odaly, O., Gilleen, J., Dominguez, M., . . . Simons, C. (2010). Functional Magnetic Resonance Imaging Of Inner Speech In Schizophrenia. Schizophrenia Research, 117(2-3), 469-470. doi:10.1016/j.schres.2010.02.883 3. Orlov, N., Giampietro, V., O’Daly, O., Barker, G., Rubia, K., Mcguire, P., . . . Allen, P. (2018). T150. Real-Time Fmri Neurofeedback To Down-Regulate Superior Temporal Gyrus Activity In Patients With Schizophrenia And Auditory Hallucinations: A Proof- Of-Concept Study. Schizophrenia Bulletin, 44(Suppl_1). doi:10.1093/schbul/sby016.426 4. Zmigrod, L., Garrison, J. R., Carr, J., & Simons, J. S. (2016). The neural mechanisms of hallucinations: A quantitative meta-analysis of neuroimaging studies. Neuroscience & Biobehavioral Reviews, 69, 113-123. doi:10.1016/j.neubiorev.2016.05.037 5. Brunelin, J., Mondino, M., Gassab, L., Haesebaert, F., Gaha, L., Suaud-Chagny, M., . . . Poulet, E. (2012). Examining Transcranial Direct-Current Stimulation (tDCS) as a Treatment for Hallucinations in Schizophrenia. American Journal of Psychiatry, 169(7), 719-724. doi:10.1176/appi.ajp.2012.11071091 6. Moseley, P., Fernyhough, C., & Ellison, A. (2014). The role of the superior temporal lobe in auditory false perceptions: A transcranial direct current stimulation study. Neuropsychologia, 62, 202-208. Doi:10.1016/j.neuropsychologia.2014.07.032 Please contact suragbhai.gohel@kernmedical.com for further inquiry regarding references. References

Cui et al [1]

Brunelin et al [5]

Shergill et al [2]

- Functional MRI (fMRI) - Resting-state fMRI (rs-fMRI)

- Cerebral blood flow (CBF) - Diffuse tensor imaging (DTI) - Magnetic resonance spectroscopy (MRS) - Positron emission tomography (PET)

Orlov et al [3]

Znigrod et al [4]

Moeley et al [6]

Method Extensive PubMed as well as Google scholar search using the words of “Schizophrenia neuroimaging”, “Schizophrenia fMRI”, “Schizophrenia diffuse tensor imaging”, “Schizophrenia transcranial magnetic stimulation” and “Auditory verbal hallucination neuroimaging” was performed. Total of 30 studies encompassing various modalities such as rs-MRI, fMRI, CBF, DTI, magnetic resonance spectroscopy and PET scans were analyzed.

Results

Anatomical Abnormality

Abnormalities of Connectivity

Baseline Activity Abnormality

Eight of our studies emphasized abnormalities of connectivity stemming from the left temporal lobe in AVH prone patients with schizophrenia. Utilizing diffuse tensor imaging on 27 patients with schizophrenia and 27 controls, a statistically significant reduction of functional connectivity (FC) in the left MTG was discovered. Comparison of three groups of patients (27 AVH-prone schizophrenia patients, 14 without AVH, and 28 healthy controls) using rs-fMRI to analyze the FC of left Heschl’s gyrus (HG) revealed hallucination severity is positively correlated to the FC between left HG and multiple areas including Broca’s area and left lateral STG. No such differences were found in the right HG. Most profound were the transcranial direct current stimulation (tDCS) studies implementing true tDCS sessions vs. sham sessions. All the studies demonstrated significant reductions of AVH in patients after receiving tDCS sessions targeting the left temporal lobe.

Ten of our studies utilizing fMRI, DTI with arterial spin labeling and MRS revealed statistically significant findings regarding abnormal baseline activity within the left temporal lobe. A large meta-analysis of fMRI and PET scan studies concluded that AVH-prone patients demonstrate a marked increase of activity in the left STG compared to healthy controls. Functional MRI imaging completed during episodes of inner speech revealed higher levels of left STG activity in AVH-prone patients vs. healthy controls. Cerebral blood flow studies revealed increased perfusion patterns within the left temporal lobe in schizophrenia patients with AVH. Magnetic resonance spectroscopy studies revealed abnormal baseline metabolic shifts in such AVH prone patients and specifically, within the left STG the shift in metabolism was statistically significant for a positive correlation to higher hallucination scores. Most intriguing, real-time fMRI neurofeedback performed on schizophrenia patients with AVH was able to attenuate the increased baseline activity within the left STG resulting in a statistically significant reduction of PSYRATS scores.

Twelve studies encompassing the use of standard MRI, fMRI, and DTI discovered statistically significant anatomical abnormalities of the brains of schizophrenia patients with AVH. These patients exhibited reductions of grey matter volume of the left temporal lobe. Two of these eleven studies are meta analysis studies whose data included results of over 400+ schizophrenia patients each and discovered statistically significant decreases of the left middle temporal gyrus (L MTG) cortical thickness in AVH subjects vs. non-AVH subjects and healthy controls. Furthermore, cortical thickness was determined to be inversely correlated with AVH severity. AVH severity was also significantly associated with grey matter reductions of the bilateral superior temporal gyri (STG), albeit only the left STG was statistically significant. Of the 12 studies, 8 consistently demonstrated a correlation between volume reduction of the left temporal gyri and increased severity of the AVH in the patients.

123