Despite the advances in pharmacotherapy for treating some psychiatric disorders like anxiety disorders, obsessive-compulsive disorder, depression, and schizophrenia, many patients become refractory and will not respond to pharmacologic treatments. Clinicians are beginning to reconsider neuromodulation surgery as a last resort for the treatment of these patients. Neurosurgical interventions aimed at treating psychiatric disorders are grouped into destructive (ablative psychosurgery) or selective stimulation (neuromodulation psychosurgery). Neuromodulation surgery involves implanting a device in the brain that modulates the neural networks within the brain.

The use of surgery for the treatment of psychiatric diseases is not a new concept. Historically, the concept of psychosurgery always raised general skepticism and stigma because of the way that it was used in the past with a high rate of complications and mortalities, but usually with little improvement in patients’ functionality. In 1881, Gottlieb Burckhardt, a Swiss psychiatrist, reported on six patients that he performed surgery to treat aggressive behavior and hallucinations with partial results. Three decades later, Puusepp operated in 1910 on three manic-depressive patients by interrupting the frontal fibers to the parietal cortex. Fulton and Jacobsen's classical experiments on two chimpanzees that received frontal lobe surgical ablation to improve neurotic behaviors were an inspiration for subsequent human ablative procedures. In 1935, a Portuguese neurologist named Egas Moniz first introduced a surgical procedure called prefrontal leucotomy. Moniz believed that abnormal connections to the frontal lobe caused some psychiatric problems and that surgically removing the white fibers connecting the frontal lobe with the rest of the brain will help mental health conditions. Moniz technique was later widely utilized in Europe and the United States. Moniz was awarded the Nobel Prize in 1949 for his contributions. In the United States, prefrontal leucotomy was initially used, but modified by an American neurosurgeon named Walter Freeman, who developed a transorbital leucotomy procedure. Unlike the original lobotomy that involved an open surgery, transorbital leucotomy was a minor surgery. It lasted about 10 to 20 minutes and aimed at separating the frontal lobe from the thalamus by accessing the brain through the back of the orbits with a sharp instrument similar to an ice pick. Clinicians often used this treatment even though, at the time, there was not much data to evaluate the effectiveness of this method, and because of the lack of alternative treatment for patients who had debilitating mental health problems. Later, retrospective studies showed that while Dr. Freeman's approach helped calmed some severely agitated patients, many ended up with numerous complications.

In the late 1950s, pharmacotherapy was introduced and changed the approach in treating psychiatric conditions. Chlorpromazine was the first U.S. Food and Drug Administration approved psychotropic drug. While pharmacotherapy led to psychosurgery quietus, physicians laid the groundwork for the development of stereotactical microsurgery techniques. Speigel and Wycis developed the concept of stereotactic surgery to perform precise ablative lesions in deep areas of the brain in 1947. In 1962, Foltz and White used this technique for stereotactic anterior cingulotomy. Furthermore, the rapid development of numerous modalities helped to understand the structure and function of the brain. These new advances, coupled with the frustrations of the significant percentage of patients not responding to pharmacotherapy and positive results in the use of neuromodulation surgery like deep brain stimulation (DBS) in the treatment of movement disorders like Parkinson's disease, leaded clinicians to revisit the use of neuromodulation surgery for the treatment of psychiatric disorders. However, professionals debated whether these techniques will be used only as a last resort for the treatment of refractory psychiatric symptoms, or if they will be used for other purposes like to modify the cognition of healthy individuals. Ethical requirements and guidelines for the procedures began to appear in physician's societies.

Purpose: The presence of verbal auditory hallucinations is often associated with psychotic disorders and rarely is considered as an ictal phenomena. The aim of this paper is to describe the anatomical structures involved in the genesis of this ictal symptom during epileptic seizures and direct cortical stimulation using stereo encephalography (SEEG).

Method: The case is of a 31-year-old right-handed female, bilateral speech representation, schizophrenia and with drug-resistant epilepsy and focal aware sensory seizures characterized by ictal verbal auditory hallucinations. She was implanted with depth electrodes, and she was monitored using SEEG recordings.

Results: She had focal aware sensory seizures characterized by verbal auditory hallucinations, with the following features: hearing numerous voices (both male and/or female), talking at the same time (not able to distinguish how many). The voices were inside her head, consisted of negative content, and lasted up to two minutes. Some of her focal aware sensory seizures evolved to focal motor seizures and rarely progressed to bilateral tonic clonic seizures. Her neurological examination, her brain MRI and her interictal SPECT were unremarkable. Her PET scan identified mild hypo metabolism over the right temporal and right frontal lobes. Her neuropsychological evaluation showed language laterality undetermined but her functional MRI showed bilateral language representation. On her video-EEG, three seizures were captured with a right posterior temporal onset. A subsequent SEEG showed thirteen typical seizures originating from the posterior temporal neocortical region. The cortical stimulation of the right posterior temporo-parietal neocortical region and right amygdala triggered her typical phenomena, which was multiple voices, inside her head, speaking in the second person, negative content, unable to identify gender, in English, and no side lateralization.

Conclusion: Verbal auditory hallucinations should be analyzed carefully because they can be part of the seizure presentation. Our case supports the localization of these hallucinations in the right posterior neocortical temporal regions.

Most mental disorders, such as addictive diseases or schizophrenia, are characterized by impaired cognitive function and behavior control originating from disturbances within prefrontal neural networks. Their often chronic reoccurring nature and the lack of efficient therapies necessitate the development of new treatment strategies. Brain-computer interfaces, equipped with multiple sensing and stimulation abilities, offer a new toolbox whose suitability for diagnosis and therapy of mental disorders has not yet been explored. This study, therefore, aimed to develop a biocompatible and multimodal neuroprosthesis to measure and modulate prefrontal neurophysiological features of neuropsychiatric symptoms. We used a 3D-printing technology to rapidly prototype customized bioelectronic implants through robot-controlled deposition of soft silicones and a conductive platinum ink. We implanted the device epidurally above the medial prefrontal cortex of rats and obtained auditory event-related brain potentials in treatment-naïve animals, after alcohol administration and following neuromodulation through implant-driven electrical brain stimulation and cortical delivery of the anti-relapse medication naltrexone. Towards smart neuroprosthetic interfaces, we furthermore developed machine learning algorithms to autonomously classify treatment effects within the neural recordings. The neuroprosthesis successfully captured neural activity patterns reflecting intact stimulus processing and alcohol-induced neural depression. Moreover, implant-driven electrical and pharmacological stimulation enabled successful enhancement of neural activity. A machine learning approach based on stepwise linear discriminant analysis was able to deal with sparsity in the data and distinguished treatments with high accuracy. Our work demonstrates the feasibility of multimodal bioelectronic systems to monitor, modulate and identify healthy and affected brain states with potential use in a personalized and optimized therapy of neuropsychiatric disorders.

Optogenetics, the use of light to control the activity of suitably sensitized cells, has led to major advances in the field of basic neuroscience since it first emerged in 2005. Already, the technique has entered clinical trials for conditions such as Retinitis Pigmentosa. A major focus of interest is the use of optogenetics within the brain, where the ability to precisely control the activity of specific subsets of neurons could lead to novel treatments for a wide range of disorders from epilepsy to schizophrenia. However, since any therapy would require both the use of gene therapy techniques to introduce non-human proteins, and implantable electronic devices to provide optical stimulation, applying this technique in the brain presents a unique set of obstacles and challenges. This review looks at the reasons why researchers are exploring the use of optogenetics within the brain. It then explores the challenges facing scientists, engineers and clinicians wanting to take this technology from the lab into the first human brain, discussing different possibilities for a first-in-human clinical trial from a sponsor, patient and regulatory perspective.

Neurotransmitters are important chemical messengers in the nervous system that play a crucial role in physiological and physical health. Abnormal levels of neurotransmitters have been correlated with physical, psychotic, and neurodegenerative diseases such as Alzheimer's, Parkinson's, dementia, addiction, depression, and schizophrenia. Although multiple neurotechnological approaches have been reported in the literature, the detection and monitoring of neurotransmitters in the brain remains a challenge and continues to garner significant attention. Neurotechnology that provides high-throughput, as well as fast and specific quantification of target analytes in the brain, without negatively impacting the implanted region is highly desired for the monitoring of the complex intercommunication of neurotransmitters. Therefore, it is crucial to develop clinical assessment techniques that are sensitive and reliable to monitor and modulate these chemical messengers and screen diseases. This review focuses on summarizing the current electrochemical measurement techniques that are capable of sensing neurotransmitters with high temporal resolution in real time. Advanced neurotransmitter sensing platforms that integrate nanomaterials and biorecognition elements are explored.