Mapping pain activation and connectivity of the human habenula

Abstract

The habenula, located in the posterior thalamus, is implicated in a wide array of functions. Animal anatomical studies have indicated that the structure receives inputs from a number of brain regions (e.g., frontal areas, hypothalamic, basal ganglia) and sends efferent connections predominantly to the brain stem (e.g., periaqueductal gray, raphe, interpeduncular nucleus). The role of the habenula in pain and its anatomical connectivity are well-documented in animals but not in humans. In this study, for the first time, we show how high-field magnetic resonance imaging can be used to detect habenula activation to noxious heat. Functional maps revealed significant, localized, and bilateral habenula responses. During pain processing, functional connectivity analysis demonstrated significant functional correlations between the habenula and the periaqueductal gray and putamen. Probabilistic tractography was used to assess connectivity of afferent (e.g., putamen) and efferent (e.g., periaqueductal gray) pathways previously reported in animals. We believe that this study is the first report of habenula activation by experimental pain in humans. Since the habenula connects forebrain structures with brain stem structures, we suggest that the findings have important implications for understanding sensory and emotional processing in the brain during both acute and chronic pain.

Habenula functional resting-state connectivity in pediatric CRPS

“…1, A and B). Connectivity and function of the Hb have been reported in animals and humans (Hikosaka 2010;Ide and Li 2011;Beretta et al 2012;Shelton et al 2012b). The MHb receives inputs from the septum and the nucleus accumbens (NAc) and projects to the interpeduncular nucleus (IPN).…”

“…The Hb has also been linked to various psychiatric disorders such as anxiety and depression (Savitz et al 2011a(Savitz et al , 2011b(Savitz et al , 2013, which are commonly comorbid disorders with chronic pain conditions. The role of the Hb in pain processing is well documented in animals (reviewed in Shelton et al 2012a), as well as in imaging studies of acute experimental pain in humans (Shelton et al 2012b). Given that chronic pain is associated with profound sensory, emotional, and cognitive changes, the Hb may be implicated in chronification of pain disorders; however, its function in chronic pain disorders remains unknown.…”

The habenula encodes negative motivational value associated with primary punishment in humans

“…Prior fMRI investigations have been limited by the use of standard data acquisition protocols, in which a single image volume element (volumetric pixel or voxel) is typically as large as the habenula itself. This low resolution, exacerbated by substantial spatial smoothing during standard data processing, is likely to induce localization error (9), rendering a signal from the habenula difficult to resolve from adjacent structures, such as the medial dorsal (MD) nucleus of the thalamus (10)(11)(12). Here, by using high-resolution fMRI, in conjunction with computational modeling of reinforcement learning in a paradigm that included…”

Acupuncture: Emerging evidence for its use as an analgesic (Review)

“…Acupuncture-induced effects interact with and coordinate different levels of the CNS. The effect of acupuncture-induced analgesia is considered to be a complicated process (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30).…”

“…These substances may be central for improving the efficacy of acupuncture-induced analgesia. Habenula nuclei serve key functions in monitoring pain, and activation of these structures may result in the inhibition of the raphe nuclei, which may in turn excite the locus coeruleus (20,21). Norepinephrine and acetylcholine are generated from the locus coeruleus or habenula nuclei; they can improve the activities of these nuclei by interacting with each other and are also involved in acupuncture analgesia (18,(22)(23)(24).…”