Skip to main content

Advertisement

SpringerLink
Log in

Deep Brain Stimulation of the Prelimbic Medial Prefrontal Cortex: Quantification of the Effect on Glucose Metabolism in the Rat Brain Using [18 F]FDG MicroPET

  • Research Article
  • Published:
Molecular Imaging and Biology Aims and scope Submit manuscript

Abstract

Purpose

Prefrontal cortex (PFC) deep brain stimulation (DBS) has been proposed as a therapy for addiction and depression. This study investigates changes in rat cerebral glucose metabolism induced by different DBS frequencies using μPET.

Procedures

One hour DBS of the prelimbic area (PL) of the medial PFC (mPFC) (60 Hz, 130 Hz or sham) in rats (n = 9) was followed by 2-deoxy-2-[18 F] fluoro-d-glucose ([18 F]FDG) μPET.

Results

Sixty Hz DBS elicited significant hypermetabolism in the ipsilateral PL ([18 F]FDG uptake +5.2 ± 2.3 %, p < 0.05). At 130 Hz, hypometabolism was induced in the ipsilateral PL (−2.5 ± 2.6 %, non-significant). Statistical parametric mapping revealed hypo and hypermetabolism clusters for both 60 and 130 Hz versus sham and show a certain state of alertness (increased activity in sensory and motor-related regions) mainly for 60 Hz.

Conclusions

This study suggests the potential of 60 Hz PL mPFC DBS for the treatment of disorders associated with prefrontal hypofunction.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Pizzolato G, Mandat T (2012) Deep brain stimulation for movement disorders. Front Integr Neurosci 6:2–2

    Article  PubMed Central  PubMed  Google Scholar 

  2. Bergey GK (2013) Neurostimulation in the treatment of epilepsy. Exp Neurol 244:87–95

    Article  PubMed  Google Scholar 

  3. Denys D, Mantione M, Figee M et al (2010) Deep brain stimulation of the nucleus accumbens for treatment-refractory obsessive-compulsive disorder. Arch Gen Psychiatry 67:1061

    Article  PubMed  Google Scholar 

  4. Anderson RJ, Frye MA, Abulseoud OA et al (2012) Deep brain stimulation for treatment-resistant depression: efficacy, safety and mechanisms of action. Neurosci Biobehav Rev 36:1920–1933

    Article  PubMed  Google Scholar 

  5. Kennedy SH, Giacobbe P, Rizvi SJ et al (2011) Deep brain stimulation for treatment-resistant depression: follow-up after 3 to 6 years. Am J Psychiatry 168:502–510

    Article  PubMed  Google Scholar 

  6. Howland RH, Shutt LS, Berman SR et al (2011) The emerging use of technology for the treatment of depression and other neuropsychiatric disorders. Ann Clin Psychiatry 23:48–62

    PubMed  Google Scholar 

  7. Mantione M, van de Brink W, Schuurman PR, Denys D (2010) Smoking cessation and weight loss after chronic deep brain stimulation of the nucleus accumbens. Neurosurgery 66:E218

    Article  PubMed  Google Scholar 

  8. Levy D, Shabat-Simon M, Shalev U et al (2007) Repeated electrical stimulation of reward-related brain regions affects cocaine but not “natural” reinforcement. J Neurosci 27:14179–14189

    Article  CAS  PubMed  Google Scholar 

  9. Pierce RC, Vassoler FM (2013) Deep brain stimulation for the treatment of addiction: basic and clinical studies and potential mechanisms of action. Psychopharmacology 229:487–491

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Hamani C, Nobrega JN (2012) Preclinical studies modeling deep brain stimulation for depression. Biol Psychiatry 72:916–923

    Article  PubMed  Google Scholar 

  11. Lozano AM, Lipsman N (2013) Probing and regulating dysfunctional circuits using deep brain stimulation. Neuron 77:406–424

    Article  CAS  PubMed  Google Scholar 

  12. Pelloux Y, Baunez C (2013) Deep brain stimulation for addiction: why the subthalamic nucleus should be favored. Curr. Opin, Neurobiol

    Google Scholar 

  13. Benabid AL, Benazzouz A, Hoffmann D et al (1998) Long-term electrical inhibition of deep brain targets in movement disorders. Mov Disord 13(Suppl 3):119–125

    PubMed  Google Scholar 

  14. Lipsman N, Woodside DB, Giacobbe P et al (2013) Subcallosal cingulate deep brain stimulation for treatment-refractory anorexia nervosa: a phase 1 pilot trial. Lancet 381:1361–1370

    Article  PubMed  Google Scholar 

  15. Wyckhuys T, Raedt R, Vonck K et al (2010) Comparison of hippocampal deep brain stimulation with high (130hz) and low frequency (5hz) on afterdischarges in kindled rats. Epilepsy Res 88:239–246

    Article  PubMed  Google Scholar 

  16. Wyckhuys T, Staelens S, Van Nieuwenhuyse B et al (2010) Hippocampal deep brain stimulation induces decreased rCBF in the hippocampal formation of the rat. NeuroImage 52:55–61

    Article  PubMed  Google Scholar 

  17. Hamani C, Diwan M, Macedo CE et al (2010) Antidepressant-like effects of medial prefrontal cortex deep brain stimulation in rats. Biol Psychiatry 67:117–124

    Article  PubMed  Google Scholar 

  18. Goddard GV, McIntyre DC, Leech CK (1969) A permanent change in brain function resulting from daily electrical stimulation. Exp Neurol 25:295–330

    Article  CAS  PubMed  Google Scholar 

  19. Zhang Q, Wu Z-C, Yu J-T et al (2012) Anticonvulsant effect of unilateral anterior thalamic high frequency electrical stimulation on amygdala-kindled seizures in rat. Brain Res Bull 87:221–226

    Article  PubMed  Google Scholar 

  20. Montgomery EB (2010) Deep brain stimulation programming: principles and practice. Press, Oxford University

    Google Scholar 

  21. Drevets WC (2000) Neuroimaging studies of mood disorders. Biol Psychiatry 48:813–829

    Article  CAS  PubMed  Google Scholar 

  22. Chang C-C, Yu S-C, McQuoid DR et al (2011) Reduction of dorsolateral prefrontal cortex gray matter in late-life depression. Psychiatry Res 193:1–6

    Article  PubMed Central  PubMed  Google Scholar 

  23. Qi X-R, Kamphuis W, Wang S et al (2013) Aberrant stress hormone receptor balance in the human prefrontal cortex and hypothalamic paraventricular nucleus of depressed patients. Psychoneuroendocrinology 38:863–870

    Article  CAS  PubMed  Google Scholar 

  24. Willner P, Scheel-Krüger J, Belzung C (2013) The neurobiology of depression and antidepressant action. Neurosci Biobehav Rev 37:2331–2371

    Article  CAS  PubMed  Google Scholar 

  25. Hayashi T, Ko JH, Strafella AP, Dagher A (2013) Dorsolateral prefrontal and orbitofrontal cortex interactions during self-control of cigarette craving. Proc Natl Acad Sci U S A 110:4422–4427

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Okada K, Ota T, Iida J et al (2013) Lower prefrontal activity in adults with obsessive-compulsive disorder as measured by near-infrared spectroscopy. Prog Neuropsychopharmacol Biol Psychiatry 43:7–13

    Article  PubMed  Google Scholar 

  27. Simmons AN, Matthews SC (2012) Neural circuitry of PTSD with or without mild traumatic brain injury: a meta-analysis. Neuropharmacology 62:598–606

    Article  CAS  PubMed  Google Scholar 

  28. Euston DR, Gruber AJ, McNaughton BL (2012) The role of medial prefrontal cortex in memory and decision making. Neuron 76:1057–1070

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  29. Miller EK, Freedman DJ, Wallis JD (2002) The prefrontal cortex: categories, concepts and cognition. Philos Trans R Soc Lond B Biol Sci 357:1123–1136

    Article  PubMed Central  PubMed  Google Scholar 

  30. Ballard IC, Murty VP, Carter RM et al (2011) Dorsolateral prefrontal cortex drives mesolimbic dopaminergic regions to initiate motivated behavior. J Neurosci 31:10340–10346

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Strafella AP, Paus T, Barrett J, Dagher A (2001) Repetitive transcranial magnetic stimulation of the human prefrontal cortex induces dopamine release in the caudate nucleus. J Neurosci 21:RC157

    CAS  PubMed  Google Scholar 

  32. Wyckhuys T, De Geeter N, Crevecoeur G et al (2013) Quantifying the effect of repetitive transcranial magnetic stimulation in the rat brain by μSPECT CBF scans. Brain Stimul 6:554–562

    Article  PubMed  Google Scholar 

  33. Parthoens J, Wyckhuys T, Stroobants S, Staelens S (2014) Small animal repetitive transcranial magnetic stimulation combined with [18 F]-FDG microPET to quantify the effect on glucose metabolism in the rat brain. submitted to Mol Imaging Biol

  34. Paxinos G, Watson C (2007) The rat brain in stereotaxic coordinates. Press, Academic

    Google Scholar 

  35. Deleye S, Verhaeghe J, Wyffels L et al (2014) Towards a reproducible protocol for repetitive and semi-quantitative rat brain imaging with (18) F-FDG: exemplified in a memantine pharmacological challenge. NeuroImage. doi:10.1016/j.neuroimage.2014.04.004

    PubMed  Google Scholar 

  36. Bao Q, Newport D, Chen M et al (2009) Performance evaluation of the inveon dedicated pet preclinical tomograph based on the NEMA NU-4 standards. J Nucl Med 50:401–408

    Article  PubMed Central  PubMed  Google Scholar 

  37. Schiffer WK, Mirrione MM, Dewey SL (2007) Optimizing experimental protocols for quantitative behavioral imaging with 18 F -FDG in rodents. J Nucl Med 48:277–287

    CAS  PubMed  Google Scholar 

  38. Chatton J-Y, Pellerin L, Magistretti PJ (2003) GABA uptake into astrocytes is not associated with significant metabolic cost: implications for brain imaging of inhibitory transmission. Proc Natl Acad Sci U S A 100:12456–12461

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  39. Hamani C, Dubiela FP, Soares JCK et al (2010) Anterior thalamus deep brain stimulation at high current impairs memory in rats. Exp Neurol 225:154–162

    Article  PubMed  Google Scholar 

  40. Smith GS (2012) Increased cerebral metabolism after 1 year of deep brain stimulation in Alzheimer disease. Arch Neurol 69:1141

    Article  PubMed  Google Scholar 

  41. Höflich A, Savli M, Comasco E et al (2013) Neuropsychiatric deep brain stimulation for translational neuroimaging. NeuroImage 79:30–41

    Article  PubMed  Google Scholar 

  42. Vitek JL (2002) Mechanisms of deep brain stimulation: excitation or inhibition. Mov Disord 17:S69–S72

    Article  PubMed  Google Scholar 

  43. Volkow ND, Fowler JS, Wang G-J (2003) The addicted human brain: insights from imaging studies. J Clin Invest 111:1444–1451

    Article  CAS  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

This work was funded by Antwerp University, Belgium through a Ph.D. grant for J. Parthoens, a postdoctoral position for J. Verhaeghe, an associate professor position for S. Staelens and a full professor position for S. Stroobants. S. Stroobants is also supported by Antwerp University Hospital, Belgium through a departmental position. Hardware and experimental costs are supported by an IOF PoC grant (45/FA020000/27/5823) of Antwerp University. Both funding sources had no further role in the study design or in the collection, analysis, and interpretation of the data.

Conflict of Interest

The authors report no conflicts of interest.

Author information

Authors and Affiliations

  1. Molecular Imaging Center Antwerp (MICA), University of Antwerp, Universiteitsplein 1, Wilrijk, Antwerp, 2610, Belgium

    Joke Parthoens, Jeroen Verhaeghe, Sigrid Stroobants & Steven Staelens

  2. Department of Nuclear Medicine, University Hospital Antwerp, Wilrijkstraat 10, Edegem, Antwerp, 2650, Belgium

    Sigrid Stroobants

Authors
  1. Joke Parthoens
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jeroen Verhaeghe
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sigrid Stroobants
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Steven Staelens
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Steven Staelens.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Parthoens, J., Verhaeghe, J., Stroobants, S. et al. Deep Brain Stimulation of the Prelimbic Medial Prefrontal Cortex: Quantification of the Effect on Glucose Metabolism in the Rat Brain Using [18 F]FDG MicroPET. Mol Imaging Biol 16, 838–845 (2014). https://doi.org/10.1007/s11307-014-0757-9

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11307-014-0757-9

Key words

Search

Navigation