The hypothalamus at the crossroads of psychopathology and neurosurgery

Abstract

<jats:p>The neurosurgical endeavor to treat psychiatric patients may have been part of human history since its beginning. The modern era of psychosurgery can be traced to the heroic attempts of Gottlieb Burckhardt and Egas Moniz to alleviate mental symptoms through the ablation of restricted areas of the frontal lobes in patients with disabling psychiatric illnesses. Thanks to the adaptation of the stereotactic frame to human patients, the ablation of large volumes of brain tissue has been practically abandoned in favor of controlled interventions with discrete targets.</jats:p><jats:p>Consonant with the role of the hypothalamus in the mediation of the most fundamental approach-avoidance behaviors, some hypothalamic nuclei and regions, in particular, have been selected as targets for the treatment of aggressiveness (posterior hypothalamus), pathological obesity (lateral or ventromedial nuclei), sexual deviations (ventromedial nucleus), and drug dependence (ventromedial nucleus). Some recent improvements in outcomes may have been due to the use of stereotactically guided deep brain stimulation and the change of therapeutic focus from categorical diagnoses (such as schizophrenia) to dimensional symptoms (such as aggressiveness), which are nonspecific in terms of formal diagnosis. However, agreement has never been reached on 2 related issues: 1) the choice of target, based on individual diagnoses; and 2) reliable prediction of outcomes related to individual targets. Despite the lingering controversies on such critical aspects, the experience of the past decades should pave the way for advances in the field. The current failure of pharmacological treatments in a considerable proportion of patients with chronic disabling mental disorders is reminiscent of the state of affairs that prevailed in the years before the early psychosurgical attempts.</jats:p><jats:p>This article reviews the functional organization of the hypothalamus, the effects of ablation and stimulation of discrete hypothalamic regions, and the stereotactic targets that have most often been used in the treatment of psychopathological and behavioral symptoms; finally, the implications of current and past experience are presented from the perspective of how this fund of knowledge may usefully contribute to the future of hypothalamic psychosurgery.</jats:p>

A high-resolution in vivo magnetic resonance imaging atlas of the human hypothalamic region

“…Through a vast array of neural connections, it receives input from both spinal cord and brainstem nuclei as well as corticolimbic structures. This information is integrated within dedicated hypothalamic nuclei, altered through secondary and tertiary hypothalamic relay stations and then conveyed to autonomic and limbic control centers where the appropriate physiological response is orchestrated across organ systems 3 . Apart from axonal projections, the hypothalamus further shapes the physiological response via engagement of the pituitary gland and release of hormones into the bloodstream 4 .…”

“…In addition, hemispheric and gender-specific volumes were normalized by hemispheric and total brain volume, respectively, to account for interindividual variability (Supplementary Tables 4 and 5). www.nature.com/scientificdata www.nature.com/scientificdata/ The mean absolute volume (± SD) of the segmented hypothalamus was 832.9 mm 3 (± 107.59 mm 3 ; left: 429.54 mm 3 ± 55.23 mm 3 ; right: 403.39 mm 3 ± 53.09 mm 3 ). Owing to an overall increase in brain volume, the mean volume in the male subgroup (892.5 mm 3 ± 99.5 mm 3 ; left: 459.82 mm 3 ± 51.55 mm 3 ; right: 432.64 mm 3 ± 48.90 mm 3 ) exceeded the values measured in the female subgroup (782.1 mm 3 ± 86.05 mm 3 ; left: 403.67 mm 3 ± 44.00 mm 3 ; right: 378.41 mm 3 ± 42.78 mm 3 ) (Fig.…”

Neurosurgery for Refractory Schizophrenia: A Systematic Literature Review

“…I the only case of hypothalamotomy analyzed, the authors reported that the patient had a rapid improvement in aggressiveness and resumed social interactions, 13 but this was to be expected, as the hypothalamus is considered to be associated with aggressive behavior. 14 It is important to note that, despite the improvement in the negative symptoms revealed in an anterior capsulotomy, there were improvements in the positive symptoms in all studies. Thus, the exploration of new targets based on the neurocircuitry involving schizophrenia, as well as the use of multiple targets, should be addressed, seeking to cover the full spectrum of symptoms, such as those involving the NAcc, the GP, and the VTA.…”

“…Better results with fewer side effects were possible thanks to the advances in imaging techniques and the rise of the stereotactic surgery. The surgery has enabled the location of the targets with high precision and minimal tissue damage, 4,14,48 which is noticeable when establishing a temporal line in the results presented, dividing the conventional leucotomies, as in the study by Benson et al, 15 of the procedures using a stereotactic technique.…”

Morphofunctional Alterations of the Hypothalamus and Social Behavior in Autism Spectrum Disorders

“…In addition, hypothalamic stimulation can also induce pleasurable experiences and prosocial behavior in humans [53,54]. For instance, several investigations demonstrated reduced aggressive behavior and increased social interactions after deep brain stimulation of the posteromedial hypothalamus [55].…”