“Early to bed, early to rise”: Diffusion tensor imaging identifies chronotype-specificity Jessica Rosenberg a,b, ⁎ ,1 , Ivan I. Maximov a,1 , Martina Reske a , Farida Grinberg a,b , N. Jon Shah a,b a Institute of Neuroscience and Medicine-4, Medical Imaging Physics, Forschungszentrum Jülich GmbH, 52425 Jülich, Germany b Department of Neurology, Faculty of Medicine, RWTH Aachen, JARA, 52074 Aachen, Germany abstract article info Article history: Accepted 26 July 2013 Available online 31 August 2013 Keywords: Chronotype Diffusion tensor imaging White matter Brain microstructure Sleep and wakefulness are crucial prerequisites for cognitive efficiency, the disturbances of which severely im- pact performance and mood as present e.g. after time zone traveling, in shift workers or patients with sleep or affective disorders. Based on their individual disposition to sleep and wakefulness, humans can be categorized as early (EC), late (LC) or intermediate (IC) chronotypes. While ECs tend to wake up early in the morning and find it difficult to remain awake beyond their usual bedtime, LCs go to bed late and have difficulties getting up. Beyond sleep/wake timings, chronotypes show distinct patterns of cognitive performance, gene expression, en- docrinology and lifestyle. However, little is known about brain structural characteristics potentially underlying differences. Specifically, white matter (WM) integrity is crucial for intact brain function and has been related to various lifestyle habits, suggesting differences between chronotypes. Hence, the present study draws on Dif- fusion Tensor Imaging as a powerful tool to non-invasively probe WM architecture in 16 ECs, 23 LCs and 20 ICs. Track-based spatial statistics highlight that LCs were characterized by WM differences in the frontal and tem- poral lobes, cingulate gyrus and corpus callosum. Results are discussed in terms of findings reporting late chronotypes to exhibit a chronic form of jet lag accompanied with sleep disturbances, vulnerability to depression and higher consumption of nicotine and alcohol. This study has far-reaching implications for health and the economy. Ideally, work schedules should fit in with chronotype-specificity whenever possible. © 2013 Elsevier Inc. All rights reserved. Introduction The term ‘chronotype’ refers to an endogenous, self-sustained dispo- sition towards sleep and wakefulness (Katzenberg et al., 1998; Vink et al., 2001) reflecting preferences in circadian (i.e., oscillation of about 24 h) rhythms. Chronotypes are categorized according to the circadian phase of their biological clock (Kerkhof and Van Dongen, 1996). Specifically, early chronotypes (EC) spontaneously wake up at an early hour and find it difficult to stay up late in the evening. On the other hand, late types (LC) tend to go to bed late at night and sleep late into the day. Chronotype-specificity is promoted by the interplay between neural cir- cadian and homeostatic oscillators (Borbely, 1982): the homeostatic process regulated by adenosine stemming from astrocytes (Halassa et al., 2009) steadily increases when awake and declines during sleep. The circadian rhythm originates in the suprachiasmatic nuclei (SCNs) of the anterior hypothalamus. Chronotype-specificity has been shown to be associated with gender, with a higher percentage of females being ECs (Vink et al., 2001), while high testosterone levels seem to lead to a stronger evening-orientation in young males (Randler et al., 2012). Furthermore, chronotype varies with age (Monk et al., 1997). In particular, teenagers often sleep until late morning and whereas elderly people wake up in the early morning hours. Endocrine factors were re- ported to be involved in these age-dependent changes of chronotype (Hagenauer et al., 2011). Lastly, the examination of genes contributing to inter-individual differences in sleep architecture, timing, and duration has recently received attention (Lazar et al., 2012). In particular, LCs show a much larger discrepancy between individual sleep preferences and normal work schedules – typically starting early in the day – that lead to the accumulation of a substantial sleep deficit dur- ing the working week as compared to ECs (Roenneberg et al., 2003). Moreover, LCs more frequently report poorer sleep quality, more tired- ness during the day (Giannotti et al., 2002; Taillard et al., 2003), exhibit psychological and psychosomatic disturbances (Giannotti et al., 2002), and consume more legal stimulants such as nicotine and alcohol (Adan, 1994; Mecacci and Rocchetti, 1998; Taillard et al., 1999) than ECs. For example, LCs seem to be more vulnerable to bipolar disorders in- cluding depression than ECs and intermediate chronotypes (IC, (Mecacci and Rocchetti, 1998; Wood et al., 2009)). Neurostructurally, the white matter (WM) underlying the anterior cingulate gyrus (ACC) and the cor- pus callosum are reportedly affected by these disorders (Brambilla et al., 2003; Barnea-Goraly et al., 2009). Moreover, the development of depres- sion during the period of a lifetime was shown to be associated with alterations of the white matter underlying the frontal lobes that have NeuroImage 84 (2014) 428–434 ⁎ Corresponding author at: Institute of Neuroscience and Medicine-4, Medical Imaging Physics, Forschungszentrum Jülich GmbH, 52425 Jülich, Germany. Fax: +49 2461611919. E-mail address: j.rosenberg@fz-juelich.de (J. Rosenberg). 1 Authors contributed equally. 1053-8119/$ – see front matter © 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.neuroimage.2013.07.086 Contents lists available at ScienceDirect NeuroImage journal homepage: www.elsevier.com/locate/ynimg