Deep Brain Stimulation of the Lateral Habenular Complex in Treatment-Resistant Depression

Schneider, Till; Beynon, Christopher; Sartorius, Alexander; Unterberg, Andreas; Kiening, Karl

doi:10.1227/neu.0b013e318277a5aa

Cited by 27 publications

(30 citation statements)

References 22 publications

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“…The LHb, which activates and inactivates the RMTg and VTA, respectively (Hong et al, 2011), is overactive in rat models of depression (Caldecott-Hazard et al, 1988;Shumake et al, 2003;Li et al, 2013) and depressed human patients (Morris et al, 1999;Roiser et al, 2009). Inhibition of the LHb reverses depression-like behaviors in rats (Winter et al, 2011) and the LHb has been targeted with some success in deep brain stimulation to treat treatment-resistant depression in humans (Sartorius et al, 2010;Schneider et al, 2013). Clearly, however, the RMTg, LHb, and VTA do not act alone to mediate complex behaviors and pathophysiologies but rather require interactions with numerous other brain structures, including, but not limited to, the raphe nuclei, pedunculopontine and laterodorsal tegmental nuclei, lateral hypothalamic-preoptic continuum, extended amygdala, ventral striatopallidum, septum-preoptic system, and orbitofrontal cortex (Kowski et al, 2008;Jhou et al, 2009b;Kaufling et al, 2009;Barrot and Thome, 2011;Bourdy and Barrot, 2012).…”

Section: Discussionmentioning

confidence: 99%

Modulation of Locomotor Activation by the Rostromedial Tegmental Nucleus

Lavezzi

Parsley

Zahm

2014

Neuropsychopharmacol

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The rostromedial tegmental nucleus (RMTg) is a strong inhibitor of dopamine neurons in the ventral tegmental area (VTA) reported to influence neurobiological and behavioral responses to reward omission, aversive and fear-eliciting stimuli, and certain drugs of abuse. Insofar as previous studies implicate ventral mesencephalic dopamine neurons as an essential component of locomotor activation, we hypothesized that the RMTg also should modulate locomotion activation. We observed that bilateral infusions into the RMTg of the gamma-aminobutyric acid A (GABA A ) agonist, muscimol, indeed activate locomotion. Alternatively, bilateral RMTg infusions of the GABA A receptor antagonist, bicuculline, suppress robust activations of locomotion elicited in two distinct ways: (1) by disinhibitory stimulation of neurons in the lateral preoptic area and (2) by return of rats to an environment previously paired with amphetamine administration. The possibility that suppressive locomotor effects of RMTg bicuculline infusions were due to unintended spread of drug to the nearby VTA was falsified by a control experiment showing that bilateral infusions of bicuculline into the VTA produce activation rather than suppression of locomotion. These results objectively implicate the RMTg in the regulation of locomotor activation. The effect is important because much evidence reported in the literature suggests that locomotor activation can be an involuntary behavioral expression of expectation and/or want without which the willingness to execute adaptive behaviors is impaired.

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Section: Discussionmentioning

confidence: 99%

Modulation of Locomotor Activation by the Rostromedial Tegmental Nucleus

Lavezzi

Parsley

Zahm

2014

Neuropsychopharmacol

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“…DBS of the SM itself has yet to be described; however, stimulation of the LHb, the afferent projection of the SM has been reported in only two patients, albeit with promising results (Sartorius et al, 2010, Schneider et al, 2013). Given its multiple efferent connections to serotonergic, dopaminergic and noradrenergic centers, its proposed effect on treatment resistant depression is convincing; however, because of its small size and the inability for MRI to distinguish between medial habenula (MHb) and LHb, a trajectory across the entire habenular complex must be chosen to ensure stimulation of both the LHb and its afferent projection, the SM (Schneider et al, 2013). A high degree of targeting accuracy must therefore be ensured to avoid stimulation based side effects given its close proximity to midbrain structures like the superior colliculus.…”

Section: Discussionmentioning

confidence: 99%

“…Over activation of the LHb has been implicated in the downregulation of serotonergic, noradrenergic and dopaminergic activity as well as stimulation of the HPA axis (Sartorius and Henn, 2007, Sartorius et al, 2010). To date, DBS of the LHb has been described in only two patients but with promising results (Schneider et al, 2013). Because of its size and location, direct targeting of the LHb, although feasible, requires meticulous planning to both effectively target the structure and avoid side effects (Schneider et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

“…To date, DBS of the LHb has been described in only two patients but with promising results (Schneider et al, 2013). Because of its size and location, direct targeting of the LHb, although feasible, requires meticulous planning to both effectively target the structure and avoid side effects (Schneider et al, 2013). For this reason, broader targeting of the SM, a structure not visible on conventional MRI, may be more suitable for DBS surgery; however, to our knowledge, DTI-based fiber tracking of the SM has yet to be described.…”

Section: Introductionmentioning

confidence: 99%

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Identification of the stria medullaris thalami using diffusion tensor imaging

Kochanski

Dawe

Eddelman

et al. 2016

NeuroImage: Clinical

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BackgroundDeep brain stimulation (DBS) via anatomical targeting of white matter tracts defined by diffusion tensor imaging (DTI) may be a useful tool in the treatment of pathologic neurophysiologic circuits implicated in certain disease states like treatment resistant depression (TRD). We sought to determine if DTI could be used to define the stria medullaris thalami (SM), the major afferent white matter pathway to the lateral habenula (LHb), a thalamic nucleus implicated in the pathophysiology of TRD.MethodsProbabilistic DTI was performed on ten cerebral hemispheres in five patients who underwent preoperative MRI for DBS surgery. Manual identification of the LHb on axial T1 weighted MRI was used for the initial seed region for tractography. Variations in tractography depending on chosen axial slice of the LHb and chosen voxel within the LHb were also assessed.ResultsIn all hemispheres the SM was reliably visualized. Variations in chosen axial seed slice as well as variations in single seed placement did not lead to significant changes in SM tractography.ConclusionsProbabilistic DTI can be used to visualize the SM which may ultimately provide utility for direct anatomic targeting in DBS surgery.

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“…Stimulacija habenula je nova tehnika lečenja i smatra se prilagodljivom, reverzibilnom i nedestruktivnom neurohirurškom intervencijom pogodnom za lečenje depresija, opsesivno-kompulsivnog poremećaja i turetovog sindroma (75). duboka moždana stimulacija habenule ili striae medullaris predstavlja izazov za neurohirurge (76,77). Posebna pažnja pridaje se prevenciji intrakranijalnog krvavljenja, koje se može javiti tokom postavljanja elektroda, što zahteva precizno anatomsko planiranje (37).…”

Section: Kontrola Sistema Zadovoljstva I Motornog Odgovoraunclassified

10.5937/mckg48-5899 = Functional and anatomical aspects of the habenular complex of epithalamus

Marković¹,

Ognjanović²

2014

Medicinski casopis

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UVODepitalamus (epithalamus) predstavlja deo međumozga, smešten na dorzokaudalnom delu talamusa i po svojoj anatomskoj poziciji, ali i neuronskim vezama predstavlja "raskrsnicu" na kojoj se ukrštaju putevi limbičkog sistema, bazalnih ganglija, ali i mnogi drugi neuronski krugovi. Morfološki gledano sastoji se iz epifize (gl. pinealis), habenularnih jedara (nuclei habenulae), međuhabenularne spojnice (commisura habenularum) i striae medularis. Habenularni kompleks je parna struktura epitalamusa, sastavljena iz dva jedra -medijalnog (nc. habenularis medialis -MHb) i lateralnog (nc. habenularis lateralis -lHb). to je filogenetski stara moždana struktura sa kod većine kičmenjaka jasno uočljivom asimetrijom u veličini kompleksa desne i leve strane (1). Medijalno jedro habenule izgrađeno je od gusto pakovanih nervnih ćelija koje su na osnovu svojih citoarhitektonskih karakteristika svrstane u pet subnukleusa (2), dok se u okviru lateralnog habenularnog jedra opisuje 10 subnukleusa (3). anatomska lokalizacija i veze omogućavaju jedrima habenule ulogu u regulaciji mnoštva fizioloških mehanizama, ali i u patogenezi pojedinih bolesti, kao što su depresija, shizofrenija, Parkinsonova bolest, bolesti zavisnosti i dr. (4). u ovom radu prikazuju se nova saznanja o ulozi habenularnog kompleksa u normalnim, fiziološkim procesima, kao i patogenezi psihijatrijskih oboljenja. NEURONSKE VEZE HABENULARNOG KOMPLEKSAHabenularni kompleks predstavlja glavnu vezu između bazalnih ganglija i limbičkih delova telencefalona, s jedne

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Deep Brain Stimulation of the Lateral Habenular Complex in Treatment-Resistant Depression

Cited by 27 publications

References 22 publications

Modulation of Locomotor Activation by the Rostromedial Tegmental Nucleus

Modulation of Locomotor Activation by the Rostromedial Tegmental Nucleus

Identification of the stria medullaris thalami using diffusion tensor imaging

10.5937/mckg48-5899 = Functional and anatomical aspects of the habenular complex of epithalamus

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