Skip to main content Accessibility help
×
Hostname: page-component-76fb5796d-wq484 Total loading time: 0 Render date: 2024-04-27T04:04:04.734Z Has data issue: false hasContentIssue false

2 - Functional imaging of schizophrenia

from Section I - Schizophrenia

Published online by Cambridge University Press:  10 January 2011

Godfrey D. Pearlson
Affiliation:
Olin Neuropsychiatry Research Center Institute of Living Hartford, CT, USA and Department of Psychiatry Yale University School of Medicine New Haven, CT, USA
Martha E. Shenton
Affiliation:
VA Boston Healthcare System and Brigham and Women's Hospital, Harvard Medical School
Bruce I. Turetsky
Affiliation:
University of Pennsylvania
Get access

Summary

Introduction

Functional magnetic resonance imaging (fMRI) neuroimaging investigations in schizophrenia have been used for a variety of purposes. These include shedding light on the underlying pathophysiology of the illness, understanding the neural basis of characteristic symptoms, aiding with diagnostic classification, predicting treatment outcome, and understanding the effects of risk genes for the disorder.

Many of these efforts have been complicated by the fact that no central etiopathology is known for the disorder, which is non-uniform in clinical presentation, and overlaps symptomatically with other psychiatric disorders. As well, there are many associated challenges and confounds that add variance to functional imaging data in schizophrenia, including the fact that many patients are chronically ill and routinely take multiple medications known to affect functional brain response. Due to both positive and negative schizophrenia symptoms, they may be unwilling or unable to engage fully with test procedures, especially on complex tasks requiring sustained attention. Much of the existing functional MRI literature is based on blood oxygen level-dependent (BOLD) activation differences gathered during the performance of cognitive tasks, most often those on which patients are known characteristically to perform poorly outside of the scanner. Such an approach has undoubtedly been valuable and produced a large and rich literature. However, none of the fMRI abnormalities recorded in this manner to date has proved diagnostic, and as we discuss below, illness-related performance differences can introduce unavoidable confounds in such task designs.

Type
Chapter
Information
Understanding Neuropsychiatric Disorders
Insights from Neuroimaging
, pp. 30 - 47
Publisher: Cambridge University Press
Print publication year: 2010

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Aleman, A, Kahn, R S. 2005. Strange feelings: do amygdala abnormalities dysregulate the emotional brain in schizophrenia? Prog Neurobiol 77, 283–98.Google Scholar
Allen, A J, Griss, M E, Folley, B S, Hawkins, K A and Pearlson, G D. 2009. Endophenotypes in schizophrenia: A selective review. Schizophr Res 109, 24–37.Google Scholar
Arfanakis, K, Cordes, D, Haughton, V M, et al. 2000. Combining independent component analysis and correlation analysis to probe interregional connectivity in fMRI task activation datasets. Magn Reson Imaging 18, 921–30.Google Scholar
Assaf, M, Rivkin, P R, Kuzu, C H, et al. 2006. Abnormal object recall and anterior cingulate overactivation correlate with formal thought disorder in schizophrenia. Biol Psychiatry 59, 452–9.Google Scholar
Assaf, M, Jagannathan, K, et al. 2009. Temporal sequence of hemispheric network activation during semantic processing: a functional network connectivity analysis. Brain Cogn 70, 238–46.Google Scholar
Astur, R S, St Germain, S A, Baker, E K, et al. 2005. fMRI hippocampal activity during a virtual radial arm maze. Appl Psychophysiol Biofeedback 30, 307–17.Google Scholar
Baas, D, Aleman, A, Vink, M, et al. 2008. Evidence of altered cortical and amygdala activation during social decision-making in schizophrenia. Neuroimage 40, 719–27.Google Scholar
Baddeley, A. 1992. Working memory. Science 255, 556–9.Google Scholar
Barch, D M, Berman, M G, Engle, R, et al. 2009. CNTRICS final task selection: working memory. Schizophr Bull 35, 136–52.Google Scholar
Barch, D M, Braver, T S, Cohen, A L, et al. 1998. Context processing deficits in schizophrenia. Arch Gen Psychiatry 50, 280–8.Google Scholar
Barch, D M, Carter, C S, Braver, T S, et al. 2001. Selective deficits in prefrontal cortex function in medication-naive patients with schizophrenia. Arch Gen Psychiatry 58, 280–8.Google Scholar
Barch, D M, and Smith, , E. 2008. The cognitive neuroscience of working memory: relevance to CNTRICS and schizophrenia. Biol Psychiatry 64, 11–7.Google Scholar
Barta, P E, Pearlson, G D, Powers, R E, et al. 1990. Auditory hallucinations and smaller superior temporal gyral volume in schizophrenia. Am J Psychiatry 147, 1457–62.Google Scholar
Beckmann, C F, DeLuca, M, Devlin, J T, et al. 2005. Investigations into resting-state connectivity using independent component analysis. Phil Trans R Soc Lond B Biol Sci 360, 1001–13.Google Scholar
Biswal, B B, Kylen, J and Hyde, J S. 1997. Simultaneous assessment of flow and BOLD signals in resting-state functional connectivity maps. NMR Biomed 10, 165–70.Google Scholar
Bluhm, R L, Miller, J, Lanius, R A, et al. 2007. Spontaneous low-frequency fluctuations in the BOLD signal in schizophrenic patients: anomalies in the default network. Schizophr Bull 33, 1004–12.Google Scholar
Broyd, S J, Demanuele, C, Debener, S, et al. 2009. Default-mode brain dysfunction in mental disorders: a systematic review. Neurosci Biobehav Rev 33, 279–96.Google Scholar
Calhoun, V D, Adali, T, Giuliani, N R, et al. 2006a. Method for multimodal analysis of independent source differences in schizophrenia: combining gray matter structural and auditory oddball functional data. Hum Brain Mapp 27, 47–62.Google Scholar
Calhoun, V D, Adali, T, Kiehl, K A, et al. 2006b. A method for multitask fMRI data fusion applied to schizophrenia. Hum Brain Mapp 27, 598–610.Google Scholar
Calhoun, V D, Adali, T, Pearlson, G D, et al. 2006c. Neuronal chronometry of target detection: fusion of hemodynamic and event-related potential data. Neuroimage 30, 544–53.Google Scholar
Calhoun, V D, Kiehl, K A, Liddle, P F, et al. 2004. Aberrant localization of synchronous hemodynamic activity in auditory cortex reliably characterizes schizophrenia. Biol Psychiatry 55, 842–9.Google Scholar
Calhoun, V D, Kiehl, K A and Pearlson, G D. 2008. Modulation of temporally coherent brain networks estimated using ICA at rest and during cognitive tasks. Hum Brain Mapp 29, 828–38.Google Scholar
Callicott, J H, Bertolino, A, Mattay, V S, et al. 2000. Physiological dysfunction of the dorsolateral prefrontal cortex in schizophrenia revisited. Cereb Cortex 10, 1078–92.Google Scholar
Callicott, J H, Egan, M F, Mattay, V S, et al. 2003a. Abnormal fMRI response of the dorsolateral prefrontal cortex in cognitively intact siblings of patients with schizophrenia. Am J Psychiatry 160, 709–19.Google Scholar
Callicott, J H, Mattay, V S, Bertolino, A, et al. 1999. Physiological characteristics of capacity constraints in working memory as revealed by functional MRI. Cereb Cortex 9, 20–6.Google Scholar
Callicott, J H, Mattay, V S, Verchinski, V A, et al. 2003b. Complexity of prefrontal cortical dysfunction in schizophrenia: more than up or down. Am J Psychiatry 160, 2209–15.Google Scholar
Callicott, J H, Ramsey, N F, Tallent, K, et al. 1998. Functional magnetic resonance imaging brain mapping in psychiatry: methodological issues illustrated in a study of working memory in schizophrenia. Neuropsychopharmacology 18, 186–96.Google Scholar
Callicott, J H, Straub, R E, Pezawas, L, et al. 2005. Variation in DISC1 affects hippocampal structure and function and increases risk for schizophrenia. Proc Natl Acad Sci U S A 102, 8627–32.Google Scholar
Carvalho, K N, Pearlson, G D, Astur, R S, et al. 2006. Simulated driving and brain imaging: combining behavior, brain activity, and virtual reality. CNS Spectr 11, 52–62.Google Scholar
Cohen, J D, Braver, T S, O'Reilly, R C, et al. 1996. A computational approach to prefrontal cortex, cognitive control and schizophrenia: recent developments and current challenges. Phil Trans R Soc Lond B Biol Sci 351, 1515–27.Google Scholar
Cordes, D, Haughton, V M, Arfanakis, K, et al. 2001. Frequencies contributing to functional connectivity in the cerebral cortex in “resting-state” data. Am J Neuroradiol 22, 1326–33.Google Scholar
Damoiseaux, J S, Rombouts, S A, Barkhof, F, et al. 2006. Consistent resting-state networks across healthy subjects. Proc Natl Acad Sci U S A 103, 13 848–53.Google Scholar
Luca, M, Smith, S, Stefano, N, et al. 2005. Blood oxygenation level dependent contrast resting state networks are relevant to functional activity in the neocortical sensorimotor system. Exp Brain Res 167, 587–94.Google Scholar
Demirci, O, Stevens, M C, Andresen, N C, et al. 2009. Investigation of relationships between fMRI brain networks in the spectral domain using ICA and Granger causality reveals distinct differences between schizophrenia patients and healthy controls. Neuroimage 46, 419–31.Google Scholar
D'Esposito, M, Postle, B R, Ballard, D, et al. 1999. Maintenance versus manipulation of information held in working memory: an event-related fMRI study. Brain Cogn 41, 66–86.Google Scholar
Di Giorgio, A, Blasi, G, Sambataro, F, et al. 2008. Association of the SerCys DISC1 polymorphism with human hippocampal formation gray matter and function during memory encoding. Eur J Neurosci 28, 2129–36.Google Scholar
Dosenbach, N U, Fair, D A, Miezin, F M, et al. 2007. Distinct brain networks for adaptive and stable task control in humans. Proc Natl Acad Sci U S A 104, 11 073–8.Google Scholar
Driesen, N R, Leung, H C, Calhoun, V D, et al. 2008. Impairment of working memory maintenance and response in schizophrenia: functional magnetic resonance imaging evidence. Biol Psychiatry 64, 1026–34.Google Scholar
Egan, M F, Goldberg, T E, Kolachana, B S, et al. 2001. Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia. Proc Natl Acad Sci U S A 98, 6917–22.Google Scholar
Foley, B S, Astur R, Jagannathan, K, et al. 2010. Anomalous neural circuit function in schizophrenia during a virtual Morris water task. Neuroimage 49, 3373–84.Google Scholar
Ford, J M, Gray, M, Whitfield, S L, et al. 2004. Acquiring and inhibiting prepotent responses in schizophrenia: event-related brain potentials and functional magnetic resonance imaging. Arch Gen Psychiatry 61, 119–29.Google Scholar
Ford, J M, Roach, B J, Jorgensen, K W, et al. 2009. Tuning in to the voices: a multisite FMRI study of auditory hallucinations. Schizophr Bull 35, 58–66.Google Scholar
Fransson, P. 2006. How default is the default mode of brain function? Further evidence from intrinsic BOLD signal fluctuations. Neuropsychologia 44, 2836–45.Google Scholar
Friedman, H R and Goldman-Rakic, , P S. 1994. Coactivation of prefrontal cortex and inferior parietal cortex in working memory tasks revealed by 2DG functional mapping in the rhesus monkey. J Neurosci 14, 2775–88.Google Scholar
Fuster, J M. 2006. The cognit: a network model of cortical representation. Int J Psychophysiol 60, 125–32.Google Scholar
Garrity, A G, Pearlson, G D, McKiernan, K, et al. 2007. Aberrant “default mode” functional connectivity in schizophrenia. Am J Psychiatry 164, 450–7.Google Scholar
Glahn, D C, Ragland, J D, Abramoff, A, et al. 2005. Beyond hypofrontality: a quantitative meta-analysis of functional neuroimaging studies of working memory in schizophrenia. Hum Brain Mapp 25, 60–9.Google Scholar
Goldberg, T E, Patterson, K J, Taqqu, Y, et al. 1998. Capacity limitations in short-term memory in schizophrenia: tests of competing hypotheses. Psychol Med 28, 665–73.Google Scholar
Goldberg, T E and Weinberger, , D R. 2004. Genes and the parsing of cognitive processes. Trends Cogn Sci 8, 325–35.Google Scholar
Green, M F. 1996. What are the functional consequences of neurocognitive deficits in schizophrenia? Am J Psychiatry 153, 321–30.Google Scholar
Greicius, M D, Srivastava, G, Reiss, A L, et al. 2004. Default-mode network activity distinguishes Alzheimer's disease from healthy aging: evidence from functional MRI. Proc Natl Acad Sci U S A 101, 4637–42.Google Scholar
Gusnard, D A, Akbudak, E, Shulman, G L, et al. 2001. Medial prefrontal cortex and self-referential mental activity: relation to a default mode of brain function. Proc Natl Acad Sci U S A 98, 4259–64.Google Scholar
Hall, J., Harris, J M, Sprengelmeyer, R, et al. 2004. Social cognition and face processing in schizophrenia. Br J Psychiatry 185, 169–70.Google Scholar
Harvey, P D and Keefe, , R S 2001. Studies of cognitive change in patients with schizophrenia following novel antipsychotic treatment. Am J Psychiatry 158, 176–84.Google Scholar
Heckers, S, Weiss, A P, Deckersbach, T, et al. 2004. Anterior cingulate cortex activation during cognitive interference in schizophrenia. Am J Psychiatry 161, 707–15.Google Scholar
Henik, A, Carter, C S, Salo, R, et al. 2002. Attentional control and word inhibition in schizophrenia. Psychiatry Res 110, 137–49.Google Scholar
Hoffman, R E, Anderson, A W, Varanko, M, et al. 2008. Time course of regional brain activation associated with onset of auditory/verbal hallucinations. Br J Psychiatry 193, 424–5.Google Scholar
Holt, D J, Kunkel, L, Weiss, A P, et al. 2006. Increased medial temporal lobe activation during the passive viewing of emotional and neutral facial expressions in schizophrenia. Schizophr Res 82, 153–62.Google Scholar
Jafri, M J, Pearlson, G D, Stevens, M, et al. 2008. A method for functional network connectivity among spatially independent resting-state components in schizophrenia. Neuroimage 39, 1666–81.Google Scholar
Jansma, J M, Ramsey, N F, Wee, M J, et al. 2004. Working memory capacity in schizophrenia: a parametric fMRI study. Schizophr Res 68, 159–71.Google Scholar
Johnson, M R, Morris, N A, Astur, R S, et al. 2006. A functional magnetic resonance imaging study of working memory abnormalities in schizophrenia. Biol Psychiatry 60, 11–21.Google Scholar
Karlsgodt, K H, Sun, D, Jimenez, A M, et al. 2008. Developmental disruptions in neural connectivity in the pathophysiology of schizophrenia. Dev Psychopathol 20, 1297–327.Google Scholar
Kerns, J G, Cohen, J D, MacDonald, A W, et al. 2005. Decreased conflict- and error-related activity in the anterior cingulate cortex in subjects with schizophrenia. Am J Psychiatry 162, 1833–9.Google Scholar
Kiehl, K A, Stevens, M C, Laurens, K R, et al. 2005. An adaptive reflexive processing model of neurocognitive function: supporting evidence from a large scale (n = 100) fMRI study of an auditory oddball task. Neuroimage 25, 899–915.Google Scholar
Laurens, K R, Kiehl, K A, Ngan, E T, et al. 2005. Attention orienting dysfunction during salient novel stimulus processing in schizophrenia. Schizophr Res 75, 159–71.Google Scholar
Liu, J, Kiehl, K A, Pearlson, G, et al. 2009a. Genetic determinants of target and novelty-related event-related potentials in the auditory oddball response. Neuroimage 46, 809–16.Google Scholar
Liu, J, Pearlson, G, Windemuth, A, et al. 2009b. Combining fMRI and SNP data to investigate connections between brain function and genetics using parallel ICA. Hum Brain Mapp 30, 241–55.Google Scholar
Lowe, M J, Mock, B J and Sorensen, J A 1998. Functional connectivity in single and multislice echoplanar imaging using resting-state fluctuations. Neuroimage 7, 119–32.Google Scholar
Manoach, D S 2003. Prefrontal cortex dysfunction during working memory performance in schizophrenia: reconciling discrepant findings. Schizophr Res 60, 285–98.Google Scholar
Manoach, D S, Gollub, R L, Benson, E S, et al. 2000. Schizophrenic subjects show aberrant fMRI activation of dorsolateral prefrontal cortex and basal ganglia during working memory performance. Biol Psychiatry 48, 99–109.Google Scholar
Manoach, D S, Greve, D N, Lindgren, K A, et al. 2003. Identifying regional activity associated with temporally separated components of working memory using event-related functional MRI. Neuroimage 20, 1670–84.Google Scholar
Manoach, D S, Schlaug, G, Siewert, B, et al. 1997. Prefrontal cortex fMRI signal changes are correlated with working memory load. Neuroreport 8, 545–9.Google Scholar
Marwick, K and Hall, J. 2008. Social cognition in schizophrenia: a review of face processing. Br Med Bull 88, 43–58.Google Scholar
McDonald, C, Marshall, N, Sham, P C, et al. 2006. Regional brain morphometry in patients with schizophrenia or bipolar disorder and their unaffected relatives. Am J Psychiatry 163, 478–87.Google Scholar
McKeown, M J and Sejnowski, , T J. 1998. Independent component analysis of fMRI data: examining the assumptions. Hum Brain Mapp 6, 368–72.Google Scholar
McKiernan, K A, D'Angelo, B R, Kaufman, J N and Binder, J R. 2006. I nterrupting the “stream of consciousness”: An fMRI investigation. Neuroimage 29, 1185–9.Google Scholar
McKiernan, K A, Kaufman, J N, Kucera-Thomson, J, et al. 2003. A parametric manipulation of factors affecting task-induced deactivation in functional neuroimaging. J Cogn Neurosci 15, 394–408.Google Scholar
Meda, S A, Bhattarai, M, Morris, N A, et al. 2008. An fMRI study of working memory in first-degree unaffected relatives of schizophrenia patients. Schizophr Res 104, 85–95.Google Scholar
Mesulam, M M. 1998. From sensation to cognition. Brain 121, 1013–52.Google Scholar
Meyer-Lindenberg, A, Poline, J B, Kohn, P D, et al. 2001. Evidence for abnormal cortical functional connectivity during working memory in schizophrenia. Am J Psychiatry 158, 1809–17.Google Scholar
Meyer-Lindenberg, A and Weinberger, , D R. 2006. Intermediate phenotypes and genetic mechanisms of psychiatric disorders. Nat Rev Neurosci 7, 818–27.Google Scholar
Miller, E K, Erickson, C A, Desimone, R, et al. 1996. Neural mechanisms of visual working memory in prefrontal cortex of the macaque. J Neurosci 16, 5154–67.Google Scholar
Minzenberg, M J, Laird, A R, Thelen, S, et al. 2009. Meta-analysis of 41 functional neuroimaging studies of executive function reveals dysfunction in a general-purpose cognitive control system in schizophrenia. Arch Gen Psychiatry 66, 811–22.Google Scholar
Park, S and Holzman, , P S. 1992. Schizophrenics show spatial working memory deficits. Arch Gen Psychiatry 49, 975–82.Google Scholar
Park, S, Puschel, J, Sauter, B H, et al. 1999. Spatial working memory deficits and clinical symptoms in schizophrenia: a 4-month follow-up study. Biol Psychiatry 46, 392–400.Google Scholar
Pearlson, G. 2009. Multisite collaborations and large databases in psychiatric neuroimaging: Advantages, problems, and challenges. Schizophr Bull 35, 1–2.Google Scholar
Pearlson, G D and Folley, B S. 2008a. Endophenotypes, dimensions, risks: is psychosis analogous to common inherited medical illnesses? Clin EEG Neurosci 39, 73–7.Google Scholar
Pearlson, G D and Folley, B S. 2008b. Schizophrenia, psychiatric genetics, and Darwinian psychiatry: An evolutionary framework. Schizophr Bull 34, 722–33.Google Scholar
Perlstein, W M, Carter, C S, Noll, D C, et al. 2001. Relation of prefrontal cortex dysfunction to working memory and symptoms in schizophrenia. Am J Psychiatry 158, 1105–13.Google Scholar
Petrides, M. 1995. Impairments on nonspatial self-ordered and externally ordered working memory tasks after lesions of the mid-dorsal part of the lateral frontal cortex in the monkey. J Neurosci 15, 359–75.Google Scholar
Pezawas, L, Verchinski, B A, Mattay, V S, et al. 2004. The brain-derived neurotrophic factor val66met polymorphism and variation in human cortical morphology. J Neurosci 24, 10 099–102.Google Scholar
Quintana, J, Wong, T, Ortiz-Portillo, E, et al. 2003. Right lateral fusiform gyrus dysfunction during facial information processing in schizophrenia. Biol Psychiatry 53, 1099–112.Google Scholar
Ragland, J D, Yoon, J, Minzenberg, M J, et al. 2007. Neuroimaging of cognitive disability in schizophrenia: search for a pathophysiological mechanism. Int Rev Psychiatry 19, 417–27.Google Scholar
Raichle, M E, MacLeod, A M, Snyder, A Z, et al. 2001. A default mode of brain function. Proc Natl Acad Sci USA 98, 676–82.Google Scholar
Rubia, K, Russell, T, Bullmore, E T, et al. 2001. An fMRI study of reduced left prefrontal activation in schizophrenia during normal inhibitory function. Schizophr Res 52, 47–55.Google Scholar
Rypma, B and D'Esposito, , M. 1999. The roles of prefrontal brain regions in components of working memory: effects of memory load and individual differences. Proc Natl Acad Sci U S A 96, 6558–63.Google Scholar
Seeley, W W, Menon, V, Schtazberg, A F, et al. 2007. Dissociable intrinsic connectivity networks for salience processing and executive control. J Neurosci 27, 2349–56.Google Scholar
Servan-Schreiber, D, Cohen, J D and Steingard, S. 1996. Schizophrenic deficits in the processing of context. A test of a theoretical model. Arch Gen Psychiatry 53, 1105–12.Google Scholar
Silver, H, Feldman, P, Bilker, W, et al. 2003. Working memory deficit as a core neuropsychological dysfunction in schizophrenia. Am J Psychiatry 160, 1809–16.Google Scholar
Sommer, I E, Diederen, K M, Blom, J D, et al. 2008. Auditory verbal hallucinations predominantly activate the right inferior frontal area. Brain 131, 3169–77.Google Scholar
Sternberg, S. 1966. High-speed scanning in human memory. Science 153, 652–4.Google Scholar
Sui, J, Adali, T, Pearlson, G D, et al. 2009. An ICA-based method for the identification of optimal FMRI features and components using combined group-discriminative techniques. Neuroimage 46, 73–86.Google Scholar
Surguladze, S, Russell, T, Kucharska-Pietura, K, et al. 2006. A reversal of the normal pattern of parahippocampal response to neutral and fearful faces is associated with reality distortion in schizophrenia. Biol Psychiatry 60, 423–31.Google Scholar
Tan, H Y, Callicott, J H and Weinberger, D , R. 2007. Dysfunctional and compensatory prefrontal cortical systems, genes and the pathogenesis of schizophrenia. Cereb Cortex 17, i171–81.Google Scholar
Veltman, D J, Rombouts, S A and Dolan, R J. 2003. Maintenance versus manipulation in verbal working memory revisited: an fMRI study. Neuroimage 18, 247–56.Google Scholar
Wexler, B E, Stevens, A A, Bowers, A A, et al. 1998. Word and tone working memory deficits in schizophrenia. Arch Gen Psychiatry 55, 1093–6.Google Scholar
Wible, C G, Lee, K, Molina, I, et al. 2009. fMRI activity correlated with auditory hallucinations during performance of a working memory task: data from the FBIRN consortium study. Schizophr Bull 35, 47–57.Google Scholar
Winterer, G, Coppola, R, Egan, M F, et al. 2003. Functional and effective frontotemporal connectivity and genetic risk for schizophrenia. Biol Psychiatry 54, 1181–92.Google Scholar
Yurgelun-Todd, D A, Waternaux, C M, Cohen, B M, et al. 1996. Functional magnetic resonance imaging of schizophrenic patients and comparison subjects during word production. Am J Psychiatry 153, 200–5.Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×