Limits...
Lateral habenula deep brain stimulation for personalized treatment of drug addiction.

Yadid G, Gispan I, Lax E - Front Hum Neurosci (2013)

View Article: PubMed Central - PubMed

Affiliation: The Neuropsychopharmacology Lab, The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University Ramat-Gan, Israel ; The Leslie and Susan Gonda (Goldschmied) Multidisciplinary Brain Research Center, Bar-Ilan University Ramat-Gan, Israel.

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

One of the prominent treatments is deep brain stimulation (DBS), in which implanted electrodes deliver electrical stimulation to stereotactically targeted brain regions... DBS in selected brain regions has shown significant therapeutic benefits for otherwise treatment-resistant movement disorders, including Parkinson's disease, essential tremor and Dystonia (Kringelbach et al., )... When the LHb is activated, it controls dopaminergic midbrain neurons both directly (Brinschwitz et al., ) and indirectly, via a bi-synaptic connection through the RMTg (Jhou et al., ,; Omelchenko et al., ; Balcita-Pedicino et al., ), leading to almost complete inhibition of all dopaminergic neurons (Ji and Shepard, )... In addition, a new study in rat models of depression revealed that tetanic, high-frequency DBS of the LHb suppressed synaptic activity of LHb VTA-projecting neurons and improved depressive-like behaviors (Li et al., )... This effect was similar to, though more potent than, results of pharmacological inhibition (Winter et al., ) and lesion of the LHb (Yang et al., )... This elevation in LHb activity may represent a form of homeostatic regulation on the reward system: excitatory LHb activity counteracts the robust increase in dopaminergic tone following cocaine exposure by inhibiting midbrain dopaminergic neurons, which consequently diminishes the drug's rewarding effect (Jhou et al., ; Zuo et al., )... It is notable that combined DBS of the LHB seems to be context-dependent, effectively reduced cocaine and sucrose self-administration (Friedman et al.,, )... How does the combination of low and high stimulation patterns effectively reduce cocaine-seeking behavior? Conversely, low frequency inputs from other brain circuits, including the VTA dopaminergic system, inhibit LHb activity following positive reward expectation (Fiorillo et al., )... Thus, usage of DTI prior to DBS application may be valuable as a preoperative, personalized evaluation tool... DTI biomarkers can assist in determining the prospects for heavy addicts to benefit from LHb DBS treatment, consequently increasing positive outcome... However, abnormal brain connectivity following excessive cocaine exposure may result in inferior treatment outcomes... As in many other therapies, treatment of addiction also exhibits a wide variability in longitudinal efficacy... Therefore, early identification of factors which reduce treatment efficacy can assist in establishing inclusion and exclusion criteria, and facilitate optimal patient management... This supports the use of brain imaging for monitoring cocaine-induced alterations in brain anatomy and fiber connectivity, prior to DBS treatment.

No MeSH data available.


Related in: MedlinePlus

(A) Scheme representing the main LHb afferents and efferents. Left: The LHb receives excitatory inputs from the GPi, which encode for aversion. The LHb subsequently fires to inhibit the VTA, which is the main dopaminergic source that activates the reward system. Thus, the GPi-LHb pathway creates negative reward signals. In contrast, when a positive reward is predicted or presented, the VTA activates the reward system and also inhibits its regulator, the LHb, thus encoding for positive reward signal. Right: Repeated intake of cocaine dose-dependently degenerate the main LHb-to-VTA fibers, which comprise the FR. This ceases LHb regulation of the VTA, which consequently renders LHb DBS ineffective at high doses (below). (B) Left: Effects of LHb DBS on cocaine-seeking behaviors. Rats were allowed to self-administer cocaine (FR-1 schedule; 0.5, 1 or 1.5 mg/kg; n = 15, 6, and 9, respectively). After reaching stable maintenance levels (day M), rats from each group were divided and either treated with DBS or sham (day M + DBS). 0.5 mg/kg and 1 mg/kg cocaine-exposed groups treated with DBS showed decreased active lever presses compared to the DBS-treated 1.5 mg/kg group (*p < 0.001 for both). DBS treatment was given again during the first extinction session, and extinction responding was measured for 6 days (E1 + DBS through E6). A significantly accelerated rate of extinction was found for the 0.5 and 1 mg/kg DBS-treated groups compared to respective controls (∧, # p < 0.001). No changes were found between DBS-treated and sham operated rats trained to self-administer 1.5 mg/kg cocaine. Right: Effect of LHb DBS on reinstatement. After E6, rats were reinstated to cocaine by a priming cocaine injection (10 mg/kg, i.p.) and light-cue. Rats which received DBS treatment on E1 and which self-administered either 0.5 or 1 mg/kg cocaine showed significantly reduced active lever presses compared to controls (**p < 0.005 and *p < 0.05, respectively). However, no differences were found between DBS-treated and sham-operated rats trained for 1.5 mg/kg cocaine. Values are expressed as mean ± SEM, in both graphs. (C) Effect of DBS of the LHb on levels of NR1, GluR1 and PSD95 in the VTA. Protein levels of the NR1 subunit of the NMDA receptor, GluR1 subunit of the AMPA receptor and scaffolding protein PSD95 were increased following cocaine self-administration (FR-1 schedule, 0.5 mg/kg). DBS of the LHb in cocaine-trained rats restored NR1, GluR1 and PSD95 levels to normal. This effect was specific to the glutamatergic system, since levels of the GABAA receptor β subunits (β2 and β3) remained unchanged. DBS alone did not alter levels of these proteins in the VTA (values are expressed as mean ± SEM). *p < 0.001 for cocaine-treated rats (coc) vs. control, sham-operated, DBS-treated and cocaine + DBS-treated rats (coc+DBS). (D) Cocaine-induced FR neurodegeneration. Left: Labeled LHb neurons in cocaine-treated vs. naïve rats. One day after reaching stable maintenance levels in the self-administration paradigm (FR-1 schedule; 0.5, 1 or 1.5 mg/kg; n = 3–5 per group), the amount of fluorogold-labeled LHb neurons was significantly reduced in 1.5 mg/kg cocaine-treated rats as compared to 0.5 mg/kg cocaine-treated (*p < 0.002) and naïve rats (**p < 0.001), indicating considerable neurodegeneration of the LHb-midbrain circuit at high dose cocaine. Values are expressed as mean ± SEM. Right: Correlation between total cocaine intake and labeled LHb neurons. A substantial, reverse correlation was found between the amount of labeled LHb neurons and total cocaine intake (mg/kg) (r = −0.894; p < 0.0003). (E) Statistical parametric maps of FA values for cocaine- vs. saline-treated rats. Rats were trained to self-administer cocaine (1.5 mg/kg, n = 6) or saline (n = 5) for 11 days. MRI followed by DTI analysis showed a significant increase in FA values in all regions of interest in rats which self-administered 1.5 mg/kg cocaine, compared to controls. No difference in FA values was found in the ventral posterior thalamus and the substantia nigra (served as control ROI; Lax et al., 2013). With permission from Friedman et al. (2010); Lax et al. (2013).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3860270&req=5

Figure 1: (A) Scheme representing the main LHb afferents and efferents. Left: The LHb receives excitatory inputs from the GPi, which encode for aversion. The LHb subsequently fires to inhibit the VTA, which is the main dopaminergic source that activates the reward system. Thus, the GPi-LHb pathway creates negative reward signals. In contrast, when a positive reward is predicted or presented, the VTA activates the reward system and also inhibits its regulator, the LHb, thus encoding for positive reward signal. Right: Repeated intake of cocaine dose-dependently degenerate the main LHb-to-VTA fibers, which comprise the FR. This ceases LHb regulation of the VTA, which consequently renders LHb DBS ineffective at high doses (below). (B) Left: Effects of LHb DBS on cocaine-seeking behaviors. Rats were allowed to self-administer cocaine (FR-1 schedule; 0.5, 1 or 1.5 mg/kg; n = 15, 6, and 9, respectively). After reaching stable maintenance levels (day M), rats from each group were divided and either treated with DBS or sham (day M + DBS). 0.5 mg/kg and 1 mg/kg cocaine-exposed groups treated with DBS showed decreased active lever presses compared to the DBS-treated 1.5 mg/kg group (*p < 0.001 for both). DBS treatment was given again during the first extinction session, and extinction responding was measured for 6 days (E1 + DBS through E6). A significantly accelerated rate of extinction was found for the 0.5 and 1 mg/kg DBS-treated groups compared to respective controls (∧, # p < 0.001). No changes were found between DBS-treated and sham operated rats trained to self-administer 1.5 mg/kg cocaine. Right: Effect of LHb DBS on reinstatement. After E6, rats were reinstated to cocaine by a priming cocaine injection (10 mg/kg, i.p.) and light-cue. Rats which received DBS treatment on E1 and which self-administered either 0.5 or 1 mg/kg cocaine showed significantly reduced active lever presses compared to controls (**p < 0.005 and *p < 0.05, respectively). However, no differences were found between DBS-treated and sham-operated rats trained for 1.5 mg/kg cocaine. Values are expressed as mean ± SEM, in both graphs. (C) Effect of DBS of the LHb on levels of NR1, GluR1 and PSD95 in the VTA. Protein levels of the NR1 subunit of the NMDA receptor, GluR1 subunit of the AMPA receptor and scaffolding protein PSD95 were increased following cocaine self-administration (FR-1 schedule, 0.5 mg/kg). DBS of the LHb in cocaine-trained rats restored NR1, GluR1 and PSD95 levels to normal. This effect was specific to the glutamatergic system, since levels of the GABAA receptor β subunits (β2 and β3) remained unchanged. DBS alone did not alter levels of these proteins in the VTA (values are expressed as mean ± SEM). *p < 0.001 for cocaine-treated rats (coc) vs. control, sham-operated, DBS-treated and cocaine + DBS-treated rats (coc+DBS). (D) Cocaine-induced FR neurodegeneration. Left: Labeled LHb neurons in cocaine-treated vs. naïve rats. One day after reaching stable maintenance levels in the self-administration paradigm (FR-1 schedule; 0.5, 1 or 1.5 mg/kg; n = 3–5 per group), the amount of fluorogold-labeled LHb neurons was significantly reduced in 1.5 mg/kg cocaine-treated rats as compared to 0.5 mg/kg cocaine-treated (*p < 0.002) and naïve rats (**p < 0.001), indicating considerable neurodegeneration of the LHb-midbrain circuit at high dose cocaine. Values are expressed as mean ± SEM. Right: Correlation between total cocaine intake and labeled LHb neurons. A substantial, reverse correlation was found between the amount of labeled LHb neurons and total cocaine intake (mg/kg) (r = −0.894; p < 0.0003). (E) Statistical parametric maps of FA values for cocaine- vs. saline-treated rats. Rats were trained to self-administer cocaine (1.5 mg/kg, n = 6) or saline (n = 5) for 11 days. MRI followed by DTI analysis showed a significant increase in FA values in all regions of interest in rats which self-administered 1.5 mg/kg cocaine, compared to controls. No difference in FA values was found in the ventral posterior thalamus and the substantia nigra (served as control ROI; Lax et al., 2013). With permission from Friedman et al. (2010); Lax et al. (2013).

Mentions: Excitatory innervations from the GPi send reward-related signals encoding for aversion, thus regulating LHb activity (Hong and Hikosaka, 2008; Shabel et al., 2012). When the LHb is activated, it controls dopaminergic midbrain neurons both directly (Brinschwitz et al., 2010) and indirectly, via a bi-synaptic connection through the RMTg (Jhou et al., 2009a,b; Omelchenko et al., 2009; Balcita-Pedicino et al., 2011), leading to almost complete inhibition of all dopaminergic neurons (Ji and Shepard, 2007). This reduces dopaminergic cell firing, consequently lowering motivation and reward (Matsumoto and Hikosaka, 2007) (Figure 1A). Given the pivotal role of the LHb in regulation of midbrain nuclei activity and therefore in reward-related behaviors, it was suggested that modulation of this region by DBS might be an effective therapeutic tool for psychiatric disorders, including major depression (Sartorius and Henn, 2007; Hauptman et al., 2008), and drug addiction (Luigjes et al., 2012). This hypothesis was strengthened by high-resolution MRI studies in humans, demonstrating reduced LHb volume in bipolar disorder and major depressive disorder (Savitz et al., 2011). In addition, a new study in rat models of depression revealed that tetanic, high-frequency DBS of the LHb suppressed synaptic activity of LHb VTA-projecting neurons and improved depressive-like behaviors (Li et al., 2011). This effect was similar to, though more potent than, results of pharmacological inhibition (Winter et al., 2011) and lesion of the LHb (Yang et al., 2008). Moreover, application of DBS to the LHB of two patients with treatment-resistant depression demonstrated promising outcomes (Sartorius et al., 2010; Kiening and Sartorius, 2013). These results raise the possibility that LHb DBS, and especially high-frequency stimulation, causes a transient “functional lesion” that reduces LHb inhibition of midbrain nuclei.


Lateral habenula deep brain stimulation for personalized treatment of drug addiction.

Yadid G, Gispan I, Lax E - Front Hum Neurosci (2013)

(A) Scheme representing the main LHb afferents and efferents. Left: The LHb receives excitatory inputs from the GPi, which encode for aversion. The LHb subsequently fires to inhibit the VTA, which is the main dopaminergic source that activates the reward system. Thus, the GPi-LHb pathway creates negative reward signals. In contrast, when a positive reward is predicted or presented, the VTA activates the reward system and also inhibits its regulator, the LHb, thus encoding for positive reward signal. Right: Repeated intake of cocaine dose-dependently degenerate the main LHb-to-VTA fibers, which comprise the FR. This ceases LHb regulation of the VTA, which consequently renders LHb DBS ineffective at high doses (below). (B) Left: Effects of LHb DBS on cocaine-seeking behaviors. Rats were allowed to self-administer cocaine (FR-1 schedule; 0.5, 1 or 1.5 mg/kg; n = 15, 6, and 9, respectively). After reaching stable maintenance levels (day M), rats from each group were divided and either treated with DBS or sham (day M + DBS). 0.5 mg/kg and 1 mg/kg cocaine-exposed groups treated with DBS showed decreased active lever presses compared to the DBS-treated 1.5 mg/kg group (*p < 0.001 for both). DBS treatment was given again during the first extinction session, and extinction responding was measured for 6 days (E1 + DBS through E6). A significantly accelerated rate of extinction was found for the 0.5 and 1 mg/kg DBS-treated groups compared to respective controls (∧, # p < 0.001). No changes were found between DBS-treated and sham operated rats trained to self-administer 1.5 mg/kg cocaine. Right: Effect of LHb DBS on reinstatement. After E6, rats were reinstated to cocaine by a priming cocaine injection (10 mg/kg, i.p.) and light-cue. Rats which received DBS treatment on E1 and which self-administered either 0.5 or 1 mg/kg cocaine showed significantly reduced active lever presses compared to controls (**p < 0.005 and *p < 0.05, respectively). However, no differences were found between DBS-treated and sham-operated rats trained for 1.5 mg/kg cocaine. Values are expressed as mean ± SEM, in both graphs. (C) Effect of DBS of the LHb on levels of NR1, GluR1 and PSD95 in the VTA. Protein levels of the NR1 subunit of the NMDA receptor, GluR1 subunit of the AMPA receptor and scaffolding protein PSD95 were increased following cocaine self-administration (FR-1 schedule, 0.5 mg/kg). DBS of the LHb in cocaine-trained rats restored NR1, GluR1 and PSD95 levels to normal. This effect was specific to the glutamatergic system, since levels of the GABAA receptor β subunits (β2 and β3) remained unchanged. DBS alone did not alter levels of these proteins in the VTA (values are expressed as mean ± SEM). *p < 0.001 for cocaine-treated rats (coc) vs. control, sham-operated, DBS-treated and cocaine + DBS-treated rats (coc+DBS). (D) Cocaine-induced FR neurodegeneration. Left: Labeled LHb neurons in cocaine-treated vs. naïve rats. One day after reaching stable maintenance levels in the self-administration paradigm (FR-1 schedule; 0.5, 1 or 1.5 mg/kg; n = 3–5 per group), the amount of fluorogold-labeled LHb neurons was significantly reduced in 1.5 mg/kg cocaine-treated rats as compared to 0.5 mg/kg cocaine-treated (*p < 0.002) and naïve rats (**p < 0.001), indicating considerable neurodegeneration of the LHb-midbrain circuit at high dose cocaine. Values are expressed as mean ± SEM. Right: Correlation between total cocaine intake and labeled LHb neurons. A substantial, reverse correlation was found between the amount of labeled LHb neurons and total cocaine intake (mg/kg) (r = −0.894; p < 0.0003). (E) Statistical parametric maps of FA values for cocaine- vs. saline-treated rats. Rats were trained to self-administer cocaine (1.5 mg/kg, n = 6) or saline (n = 5) for 11 days. MRI followed by DTI analysis showed a significant increase in FA values in all regions of interest in rats which self-administered 1.5 mg/kg cocaine, compared to controls. No difference in FA values was found in the ventral posterior thalamus and the substantia nigra (served as control ROI; Lax et al., 2013). With permission from Friedman et al. (2010); Lax et al. (2013).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3860270&req=5

Figure 1: (A) Scheme representing the main LHb afferents and efferents. Left: The LHb receives excitatory inputs from the GPi, which encode for aversion. The LHb subsequently fires to inhibit the VTA, which is the main dopaminergic source that activates the reward system. Thus, the GPi-LHb pathway creates negative reward signals. In contrast, when a positive reward is predicted or presented, the VTA activates the reward system and also inhibits its regulator, the LHb, thus encoding for positive reward signal. Right: Repeated intake of cocaine dose-dependently degenerate the main LHb-to-VTA fibers, which comprise the FR. This ceases LHb regulation of the VTA, which consequently renders LHb DBS ineffective at high doses (below). (B) Left: Effects of LHb DBS on cocaine-seeking behaviors. Rats were allowed to self-administer cocaine (FR-1 schedule; 0.5, 1 or 1.5 mg/kg; n = 15, 6, and 9, respectively). After reaching stable maintenance levels (day M), rats from each group were divided and either treated with DBS or sham (day M + DBS). 0.5 mg/kg and 1 mg/kg cocaine-exposed groups treated with DBS showed decreased active lever presses compared to the DBS-treated 1.5 mg/kg group (*p < 0.001 for both). DBS treatment was given again during the first extinction session, and extinction responding was measured for 6 days (E1 + DBS through E6). A significantly accelerated rate of extinction was found for the 0.5 and 1 mg/kg DBS-treated groups compared to respective controls (∧, # p < 0.001). No changes were found between DBS-treated and sham operated rats trained to self-administer 1.5 mg/kg cocaine. Right: Effect of LHb DBS on reinstatement. After E6, rats were reinstated to cocaine by a priming cocaine injection (10 mg/kg, i.p.) and light-cue. Rats which received DBS treatment on E1 and which self-administered either 0.5 or 1 mg/kg cocaine showed significantly reduced active lever presses compared to controls (**p < 0.005 and *p < 0.05, respectively). However, no differences were found between DBS-treated and sham-operated rats trained for 1.5 mg/kg cocaine. Values are expressed as mean ± SEM, in both graphs. (C) Effect of DBS of the LHb on levels of NR1, GluR1 and PSD95 in the VTA. Protein levels of the NR1 subunit of the NMDA receptor, GluR1 subunit of the AMPA receptor and scaffolding protein PSD95 were increased following cocaine self-administration (FR-1 schedule, 0.5 mg/kg). DBS of the LHb in cocaine-trained rats restored NR1, GluR1 and PSD95 levels to normal. This effect was specific to the glutamatergic system, since levels of the GABAA receptor β subunits (β2 and β3) remained unchanged. DBS alone did not alter levels of these proteins in the VTA (values are expressed as mean ± SEM). *p < 0.001 for cocaine-treated rats (coc) vs. control, sham-operated, DBS-treated and cocaine + DBS-treated rats (coc+DBS). (D) Cocaine-induced FR neurodegeneration. Left: Labeled LHb neurons in cocaine-treated vs. naïve rats. One day after reaching stable maintenance levels in the self-administration paradigm (FR-1 schedule; 0.5, 1 or 1.5 mg/kg; n = 3–5 per group), the amount of fluorogold-labeled LHb neurons was significantly reduced in 1.5 mg/kg cocaine-treated rats as compared to 0.5 mg/kg cocaine-treated (*p < 0.002) and naïve rats (**p < 0.001), indicating considerable neurodegeneration of the LHb-midbrain circuit at high dose cocaine. Values are expressed as mean ± SEM. Right: Correlation between total cocaine intake and labeled LHb neurons. A substantial, reverse correlation was found between the amount of labeled LHb neurons and total cocaine intake (mg/kg) (r = −0.894; p < 0.0003). (E) Statistical parametric maps of FA values for cocaine- vs. saline-treated rats. Rats were trained to self-administer cocaine (1.5 mg/kg, n = 6) or saline (n = 5) for 11 days. MRI followed by DTI analysis showed a significant increase in FA values in all regions of interest in rats which self-administered 1.5 mg/kg cocaine, compared to controls. No difference in FA values was found in the ventral posterior thalamus and the substantia nigra (served as control ROI; Lax et al., 2013). With permission from Friedman et al. (2010); Lax et al. (2013).
Mentions: Excitatory innervations from the GPi send reward-related signals encoding for aversion, thus regulating LHb activity (Hong and Hikosaka, 2008; Shabel et al., 2012). When the LHb is activated, it controls dopaminergic midbrain neurons both directly (Brinschwitz et al., 2010) and indirectly, via a bi-synaptic connection through the RMTg (Jhou et al., 2009a,b; Omelchenko et al., 2009; Balcita-Pedicino et al., 2011), leading to almost complete inhibition of all dopaminergic neurons (Ji and Shepard, 2007). This reduces dopaminergic cell firing, consequently lowering motivation and reward (Matsumoto and Hikosaka, 2007) (Figure 1A). Given the pivotal role of the LHb in regulation of midbrain nuclei activity and therefore in reward-related behaviors, it was suggested that modulation of this region by DBS might be an effective therapeutic tool for psychiatric disorders, including major depression (Sartorius and Henn, 2007; Hauptman et al., 2008), and drug addiction (Luigjes et al., 2012). This hypothesis was strengthened by high-resolution MRI studies in humans, demonstrating reduced LHb volume in bipolar disorder and major depressive disorder (Savitz et al., 2011). In addition, a new study in rat models of depression revealed that tetanic, high-frequency DBS of the LHb suppressed synaptic activity of LHb VTA-projecting neurons and improved depressive-like behaviors (Li et al., 2011). This effect was similar to, though more potent than, results of pharmacological inhibition (Winter et al., 2011) and lesion of the LHb (Yang et al., 2008). Moreover, application of DBS to the LHB of two patients with treatment-resistant depression demonstrated promising outcomes (Sartorius et al., 2010; Kiening and Sartorius, 2013). These results raise the possibility that LHb DBS, and especially high-frequency stimulation, causes a transient “functional lesion” that reduces LHb inhibition of midbrain nuclei.

View Article: PubMed Central - PubMed

Affiliation: The Neuropsychopharmacology Lab, The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University Ramat-Gan, Israel ; The Leslie and Susan Gonda (Goldschmied) Multidisciplinary Brain Research Center, Bar-Ilan University Ramat-Gan, Israel.

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

One of the prominent treatments is deep brain stimulation (DBS), in which implanted electrodes deliver electrical stimulation to stereotactically targeted brain regions... DBS in selected brain regions has shown significant therapeutic benefits for otherwise treatment-resistant movement disorders, including Parkinson's disease, essential tremor and Dystonia (Kringelbach et al., )... When the LHb is activated, it controls dopaminergic midbrain neurons both directly (Brinschwitz et al., ) and indirectly, via a bi-synaptic connection through the RMTg (Jhou et al., ,; Omelchenko et al., ; Balcita-Pedicino et al., ), leading to almost complete inhibition of all dopaminergic neurons (Ji and Shepard, )... In addition, a new study in rat models of depression revealed that tetanic, high-frequency DBS of the LHb suppressed synaptic activity of LHb VTA-projecting neurons and improved depressive-like behaviors (Li et al., )... This effect was similar to, though more potent than, results of pharmacological inhibition (Winter et al., ) and lesion of the LHb (Yang et al., )... This elevation in LHb activity may represent a form of homeostatic regulation on the reward system: excitatory LHb activity counteracts the robust increase in dopaminergic tone following cocaine exposure by inhibiting midbrain dopaminergic neurons, which consequently diminishes the drug's rewarding effect (Jhou et al., ; Zuo et al., )... It is notable that combined DBS of the LHB seems to be context-dependent, effectively reduced cocaine and sucrose self-administration (Friedman et al.,, )... How does the combination of low and high stimulation patterns effectively reduce cocaine-seeking behavior? Conversely, low frequency inputs from other brain circuits, including the VTA dopaminergic system, inhibit LHb activity following positive reward expectation (Fiorillo et al., )... Thus, usage of DTI prior to DBS application may be valuable as a preoperative, personalized evaluation tool... DTI biomarkers can assist in determining the prospects for heavy addicts to benefit from LHb DBS treatment, consequently increasing positive outcome... However, abnormal brain connectivity following excessive cocaine exposure may result in inferior treatment outcomes... As in many other therapies, treatment of addiction also exhibits a wide variability in longitudinal efficacy... Therefore, early identification of factors which reduce treatment efficacy can assist in establishing inclusion and exclusion criteria, and facilitate optimal patient management... This supports the use of brain imaging for monitoring cocaine-induced alterations in brain anatomy and fiber connectivity, prior to DBS treatment.

No MeSH data available.


Related in: MedlinePlus