Skip to main content

Advertisement

SpringerLink
Log in

Neural correlates of changes in sexual function in frontotemporal dementia: implications for reward and physiological functioning

  • Original Communication
  • Published:
Journal of Neurology Aims and scope Submit manuscript

Abstract

Background

Frontotemporal dementia (FTD) is characterised by changes in behaviour including alterations in sexual function. While hypersexual behaviour is commonly thought to predominate, emerging evidence suggests that hyposexual behaviour is in fact most prevalent. The underlying mechanisms driving these behavioural changes remain unclear; however, likely reflect interactions between cognitive, emotional, reward processing and physiological functioning. We aimed to systematically quantify changes in sexual behaviour in behavioural variant FTD (bvFTD) and semantic dementia (SD) in contrast with Alzheimer’s disease (AD) and to elucidate the neural correlates of these changes using whole-brain voxel-based morphometry.

Methods

Carers of 62 dementia patients (30 bvFTD, 12 SD, 20 AD) were interviewed using the Sexual Behaviour and Intimacy Questionnaire, which assesses changes in sexual function. Voxel-based morphometry analysis of structural MRI brain scans was used to determine the association between changes in grey matter intensity and the presence of hyposexual, hypersexual, and inappropriate sexual behaviour across groups.

Results

Widespread attenuation of sexual drive, intimacy and the display of affection were evident irrespective of dementia subtype. In contrast, hypersexual and inappropriate sexual behaviour was present in only a small proportion of patients. Neuroimaging analyses revealed an association between hyposexual behaviour and atrophy of the right supramarginal gyrus, middle frontal gyrus and thalamus, whilst hypersexual behaviour was associated with cerebellar atrophy.

Conclusion

Counter to the prevailing view, younger-onset dementia syndromes predominantly display an attenuation in sexual drive. Changes in sexual function likely reflect the degeneration of cortical and subcortical neural circuits implicated in reward, autonomic function, empathy, and emotional processing.

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

Similar content being viewed by others

References

  1. Rascovsky K, Hodges JR, Knopman D, Mendez MF, Kramer JH, Neuhaus J, van Swieten JC, Seelaar H, Dopper EG, Onyike CU, Hillis AE, Josephs KA, Boeve BF, Kertesz A, Seeley WW, Rankin KP, Johnson JK, Gorno-Tempini ML, Rosen H, Prioleau-Latham CE, Lee A, Kipps CM, Lillo P, Piguet O, Rohrer JD, Rossor MN, Warren JD, Fox NC, Galasko D, Salmon DP, Black SE, Mesulam M, Weintraub S, Dickerson BC, Diehl-Schmid J, Pasquier F, Deramecourt V, Lebert F, Pijnenburg Y, Chow TW, Manes F, Grafman J, Cappa SF, Freedman M, Grossman M, Miller BL (2011) Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain 134:2456–2477

    Article  Google Scholar 

  2. Irish M, Piguet O, Hodges JR (2011) Self-projection and the default network in frontotemporal dementia. Nat Rev Neurol 8:152–161

    Article  Google Scholar 

  3. Ahmed RM, Ke YD, Vucic S, Ittner LM, Seeley W, Hodges JR, Piguet O, Halliday G, Kiernan MC (2018) Physiological changes in neurodegeneration—mechanistic insights and clinical utility. Nat Rev Neurol 14:259–271

    Article  CAS  Google Scholar 

  4. Ahmed RM, Irish M, Piguet O, Halliday GM, Ittner LM, Farooqi S, Hodges JR, Kiernan MC (2016) Amyotrophic lateral sclerosis and frontotemporal dementia: distinct and overlapping changes in eating behaviour and metabolism. Lancet Neurol 15:332–342

    Article  Google Scholar 

  5. Ahmed RM, Latheef S, Bartley L, Irish M, Halliday GM, Kiernan MC, Hodges JR, Piguet O (2015) Eating behavior in frontotemporal dementia: peripheral hormones vs hypothalamic pathology. Neurology 85:1310–1317

    Article  Google Scholar 

  6. Baird AD, Wilson SJ, Bladin PF, Saling MM, Reutens DC (2007) Neurological control of human sexual behaviour: insights from lesion studies. J Neurol Neurosurg Psychiatry 78:1042–1049

    Article  Google Scholar 

  7. Poetter CE, Stewart JT (2012) Treatment of indiscriminate, inappropriate sexual behavior in frontotemporal dementia with carbamazepine. J Clin Psychopharmacol 32:137–138

    Article  Google Scholar 

  8. Mendez MF, Shapira JS (2011) Internet pornography and frontotemporal dementia. J Neuropsychiatry Clin Neurosci 23:E3

    Article  Google Scholar 

  9. Reeves RR, Perry CL (2013) Aripiprazole for sexually inappropriate vocalizations in frontotemporal dementia. J Clin Psychopharmacol 33:145–146

    Article  Google Scholar 

  10. Perry DC, Sturm VE, Seeley WW, Miller BL, Kramer JH, Rosen HJ (2014) Anatomical correlates of reward-seeking behaviours in behavioural variant frontotemporal dementia. Brain 137:1621–1626

    Article  Google Scholar 

  11. Mendez MF, Shapira JS (2013) Hypersexual behavior in frontotemporal dementia: a comparison with early-onset Alzheimer’s disease. Arch Sex Behav 42:501–509

    Article  Google Scholar 

  12. Kumfor F, Zhen A, Hodges JR, Piguet O, Irish M (2018) Apathy in Alzheimer’s disease and frontotemporal dementia: distinct clinical profiles and neural correlates. Cortex 103:350–359

    Article  Google Scholar 

  13. Miller BL, Darby AL, Swartz JR, Yener GG, Mena I (1995) Dietary changes, compulsions and sexual behavior in frontotemporal degeneration. Dementia 6:195–199

    CAS  PubMed  Google Scholar 

  14. Ahmed RM, Kaizik C, Irish M, Mioshi E, Dermody N, Kiernan MC, Piguet O, Hodges JR (2015) Characterizing sexual behavior in frontotemporal dementia. J Alzheimers Dis 46:677–686

    Article  Google Scholar 

  15. Hsieh S, Irish M, Daveson N, Hodges JR, Piguet O (2013) When one loses empathy: its effect on carers of patients with dementia. J Geriatr Psychiatry Neurol 26:174–184

    Article  Google Scholar 

  16. Zamboni G, Huey ED, Krueger F, Nichelli PF, Grafman J (2008) Apathy and disinhibition in frontotemporal dementia: insights into their neural correlates. Neurology 71:736–742

    Article  CAS  Google Scholar 

  17. Irish M, Hodges JR, Piguet O (2014) Right anterior temporal lobe dysfunction underlies theory of mind impairments in semantic dementia. Brain 137:1241–1253

    Article  Google Scholar 

  18. Gorno-Tempini ML, Hillis AE, Weintraub S, Kertesz A, Mendez M, Cappa SF, Ogar JM, Rohrer JD, Black S, Boeve BF, Manes F, Dronkers NF, Vandenberghe R, Rascovsky K, Patterson K, Miller BL, Knopman DS, Hodges JR, Mesulam MM, Grossman M (2011) Classification of primary progressive aphasia and its variants. Neurology 76:1006–1014

    Article  Google Scholar 

  19. McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr, Kawas CH, Klunk WE, Koroshetz WJ, Manly JJ, Mayeux R, Mohs RC, Morris JC, Rossor MN, Scheltens P, Carrillo MC, Thies B, Weintraub S, Phelps CH (2011) The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 7:263–269

    Article  Google Scholar 

  20. Mioshi E, Hsieh S, Savage S, Hornberger M, Hodges JR (2010) Clinical staging and disease progression in frontotemporal dementia. Neurology 74:1591–1597

    Article  CAS  Google Scholar 

  21. Mioshi E, Dawson K, Mitchell J, Arnold R, Hodges JR (2006) The Addenbrooke’s cognitive examination revised (ACE-R): a brief cognitive test battery for dementia screening. Int J Geriatr Psychiatry 21:1078–1085

    Article  Google Scholar 

  22. Hsieh S, Schubert S, Hoon C, Mioshi E, Hodges JR (2013) Validation of the Addenbrooke’s Cognitive Examination III in frontotemporal dementia and Alzheimer’s disease. Dement Geriatr Cogn Disord 36:242–250

    Article  Google Scholar 

  23. Wedderburn C, Wear H, Brown J, Mason SJ, Barker RA, Hodges J, Williams-Gray C (2008) The utility of the Cambridge Behavioural Inventory in neurodegenerative disease. J Neurol Neurosurg Psychiatry 79:500–503

    Article  CAS  Google Scholar 

  24. Davis M (1983) Measuring individual differences in empathy: evidence for a multidimensional approach. J Personal Soc Psychol 44:113–126

    Article  Google Scholar 

  25. Dermody N, Wong S, Ahmed R, Piguet O, Hodges JR, Irish M (2016) Uncovering the neural bases of cognitive and affective empathy deficits in Alzheimer’s disease and the behavioral-variant of frontotemporal dementia. J Alzheimers Dis 53:801–816

    Article  Google Scholar 

  26. Ashburner J, Friston KJ (2000) Voxel-based morphometry—the methods. Neuroimage 11:805–821

    Article  CAS  Google Scholar 

  27. Smith SM, Jenkinson M, Woolrich MW, Beckmann CF, Behrens TE, Johansen-Berg H, Bannister PR, De Luca M, Drobnjak I, Flitney DE, Niazy RK, Saunders J, Vickers J, Zhang Y, De Stefano N, Brady JM, Matthews PM (2004) Advances in functional and structural MR image analysis and implementation as FSL. Neuroimage 23(Suppl 1):S208–S219

    Article  Google Scholar 

  28. Smith SM (2002) Fast robust automated brain extraction. Hum Brain Mapp 17:143–155

    Article  Google Scholar 

  29. Zhang YY, Brady M, Smith S (2001) Segmentation of brain MR images through a hidden Markov random field model and the expectation-maximization algorithm. IEEE Trans Med Imaging 20:45–57

    Article  CAS  Google Scholar 

  30. Andersson JLR, Jenkinson M, Smith S (2007) Non-linear optimisation, in FMRIB Technical Report TR07JA1. University of Oxford FMRIB Centre, Oxford

    Google Scholar 

  31. Andersson JLR, Jenkinson M, Smith S (2007) Non-linear registration, aka spatial normalisation, in FMRIB Technical Report TR07JA2. University of Oxford FMRIB Centre, Oxford

    Google Scholar 

  32. Rueckert D, Sonoda LI, Hayes C, Hill DLG, Leach MO, Hawkes DJ (1999) Nonrigid registration using free-form deformations: application to breast MR images. IEEE Trans Med Imaging 18:712–721

    Article  CAS  Google Scholar 

  33. Nichols TE, Holmes AP (2002) Nonparametric permutation tests for functional neuroimaging: a primer with examples. Hum Brain Mapp 15:1–25

    Article  Google Scholar 

  34. Lieberman MD, Cunningham WA (2009) Type I and Type II error concerns in fMRI research: re-balancing the scale. Soc Cogn Affect Neurosci 4:423–428

    Article  Google Scholar 

  35. Silani G, Lamm C, Ruff CC, Singer T (2013) Right supramarginal gyrus is crucial to overcome emotional egocentricity bias in social judgments. J Neurosci 33:15466–15476

    Article  CAS  Google Scholar 

  36. Saxe R, Wexler A (2005) Making sense of another mind: the role of the right temporo-parietal junction. Neuropsychologia 43:1391–1399

    Article  Google Scholar 

  37. Japee S, Holiday K, Satyshur MD, Mukai I, Ungerleider LG (2015) A role of right middle frontal gyrus in reorienting of attention: a case study. Front Syst Neurosci 9:23

    Article  Google Scholar 

  38. Komura Y, Tamura R, Uwano T, Nishijo H, Kaga K, Ono T (2001) Retrospective and prospective coding for predicted reward in the sensory thalamus. Nature 412:546–549

    Article  CAS  Google Scholar 

  39. Chakraborty S, Kolling N, Walton ME, Mitchell AS (2016) Critical role for the mediodorsal thalamus in permitting rapid reward-guided updating in stochastic reward environments. eLife 5:e13588

    Article  Google Scholar 

  40. Ahmed RM, Irish M, Henning E, Dermody N, Bartley L, Kiernan MC, Piguet O, Farooqi S, Hodges JR (2016) Assessment of eating behavior disturbance and associated neural networks in frontotemporal dementia. JAMA Neurol 73:282–290

    Article  Google Scholar 

  41. Fletcher PD, Downey LE, Golden HL, Clark CN, Slattery CF, Paterson RW, Rohrer JD, Schott JM, Rossor MN, Warren JD (2015) Pain and temperature processing in dementia: a clinical and neuroanatomical analysis. Brain 138:3360–3372

    Article  Google Scholar 

  42. Kullmann S, Heni M, Linder K, Zipfel S, Haring HU, Veit R, Fritsche A, Preissl H (2014) Resting-state functional connectivity of the human hypothalamus. Hum Brain Mapp 35:6088–6096

    Article  Google Scholar 

  43. Schmahmann JD (2016) Cerebellum in Alzheimer’s disease and frontotemporal dementia: not a silent bystander. Brain 139:1314–1318

    Article  Google Scholar 

  44. Synn A, Mothakunnel A, Kumfor F, Chen Y, Piguet O, Hodges JR, Irish M (2018) Mental states in moving shapes: distinct cortical and subcortical contributions to theory of mind impairments in dementia. J Alzheimers Dis 61:521–535

    Article  Google Scholar 

  45. Wagner MJ, Kim TH, Savall J, Schnitzer MJ, Luo L (2017) Cerebellar granule cells encode the expectation of reward. Nature 544:96–100

    Article  CAS  Google Scholar 

  46. Guo CC, Tan R, Hodges JR, Hu X, Sami S, Hornberger M (2016) Network-selective vulnerability of the human cerebellum to Alzheimer’s disease and frontotemporal dementia. Brain 139:1527–1538

    Article  Google Scholar 

  47. Grahn JA, Parkinson JA, Owen AM (2008) The cognitive functions of the caudate nucleus. Prog Neurobiol 86:141–155

    Article  Google Scholar 

  48. Hillis AE (2014) Inability to empathize: brain lesions that disrupt sharing and understanding another’s emotions. Brain 137:981–997

    Article  Google Scholar 

  49. O’Connor CM, Clemson L, Hornberger M, Leyton CE, Hodges JR, Piguet O, Mioshi E (2016) Longitudinal change in everyday function and behavioral symptoms in frontotemporal dementia. Neurol Clin Pract 6:419–428

    Article  Google Scholar 

Download references

Funding

This work was supported in part by funding to Forefront, a collaborative research group dedicated to the study of frontotemporal dementia and amyotrophic lateral sclerosis, from the National Health and Medical Research Council of Australia (NHMRC) programme grant (#1037746 to MK and JH) and the Australian Research Council Centre of Excellence in Cognition and its Disorders Memory Program (#CE110001021 to OP and JH). We are grateful to the research participants involved with the ForeFront research studies. RA is a NHMRC Early Career Fellow (#1120770). OP is a NHMRC Senior Research Fellow (#1103258). MI is supported by an Australian Research Council Future Fellowship (FT160100096).

Author information

Authors and Affiliations

  1. ForeFront Clinic, Sydney Medical School, Brain and Mind Centre, The University of Sydney, 94 Mallett St Camperdown, Sydney, NSW, 2050, Australia

    Rebekah M. Ahmed, Cassandra Kaizik, Matthew C. Kiernan & John R. Hodges

  2. Memory and Cognition Clinic, Institute of Clinical Neurosciences, Royal Prince Alfred Hospital, Sydney, Australia

    Rebekah M. Ahmed, Cassandra Kaizik & Matthew C. Kiernan

  3. School of Psychology and Brain and Mind Centre, The University of Sydney, Sydney, Australia

    Zoë-lee Goldberg, Olivier Piguet & Muireann Irish

  4. ARC Centre of Excellence in Cognition and its Disorders, Sydney, Australia

    John R. Hodges, Olivier Piguet & Muireann Irish

Authors
  1. Rebekah M. Ahmed
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zoë-lee Goldberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Cassandra Kaizik
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Matthew C. Kiernan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. John R. Hodges
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Olivier Piguet
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Muireann Irish
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rebekah M. Ahmed.

Ethics declarations

Conflicts of interest

No author reports any conflict of interest. MCK is Editor in chief of Journal of Neurology Neurosurgery and Psychiatry.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 26 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ahmed, R.M., Goldberg, Zl., Kaizik, C. et al. Neural correlates of changes in sexual function in frontotemporal dementia: implications for reward and physiological functioning. J Neurol 265, 2562–2572 (2018). https://doi.org/10.1007/s00415-018-9024-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-018-9024-3

Keywords

Search

Navigation