Christof Karmonik, PhD Mario Dulay, PhD Amit Verma, MD Robert G. Grossman, MD

Christof Karmonik, PhD Mario Dulay, PhD Amit Verma, MD Robert G. Grossman, MD

Specific set of brain regions engaged when subject are engaged on internally focused tasks Autobiographical memory retrieval Envisioning future events Day dreaming. Default network (Shulman 1997, Mazoyer, 2001, Raichle 2001)

Discovery accidental Investigation of Brain activity during unidirectional mental states included rest state (mental control) Activity increase in rest state compared to goal directed behavior At fist, analysis was afterthought

James (1890): Modulation of local blood flow by mental activity Sokoloff (1955): No change in total brain metabolism between rest state and arithmetic problem thinking => vigorous brain activity when resting Ingvar (1979): increased frontal lobe activity during rest states Hyperfrontal activity pattern during rest (average over 8 subjects) Ingvar 1979 Xenon 133 inhalation technique

Functional Brain imaging using PET Better resolution and higher sensitivity to deep brain structures Short half lives=>many task and control states Research studies note deactivation One possible cause: activity reduction in unattended sensory modalities Another possible cause: higher brain activation in rest state than control state (frontal and posterior midline) Andreason (1995): Similar brain regions activated during rest and memory task (recollection of past events, planning of future activity): prefrontal midline region, posterior cingulate, retrosplenial cortex

Shulman (1997): 132 normal adults (direct comparison of active task to passive task (no goal) Mazoyer (2001): 63 normal adults (visually and aurally cued task compared to rest condition) Analyses created the term Default Network Consistent number of brain regions active during passive (or rest) state Rest state associated with lively mental activity Meta Analysis of 9 PET studies showing Regions most active during passive task Shulman 1997) subject averaged brain surface

Raichle, Gusnard (2001): Empirical and theoretical implications of defining a default baseline state Medial prefrontal regions: selfreferring processing Default network is a fundamental neurobiological system with its own properties (such as the motor or visual system)

Buckner et al 2008

All neuroimaging approaches converged at a similar estimate of the anatomy of the DN Intrinsic Architecture of DN suggests multiple interacting switches and subsystems PET block design (see above) fmri block and event related design (randomly spaced epochs of rest with different length of several seconds): DN activation potentially dependent on length of passive epoch

fmri data (Shannon 2006) Buckner et al 2008

Measurement of brain s intrinsic activity From individual neurons, cortical columns to whole brain systems: spontaneous activity present tracking the functional and anatomical organization of the brain Patterns of spontaneity are believed to reflect direct and indirect anatomical connectivity Functional connectivity MRI (Biswal 1995) Independent of task induced deactivation Greicius at al (2003, 2004): DN includes hippocampus and adjacent areas in temporal medial lobe associated with episodic memory

Buckner et al 2008

Blue: medial temporal Lobe subsystem Red: core system Buckner et al 2008 Lower correlations medial temporal lobe subsystem Presently unclear Infants do not show these interaction, development Occurs in toddler age or later (Fransson, 2007)

Greicius, Menon (2004): Spontaneous activity correlation in the DN persists during active states (alternating rest and visual or auditory stimuli) Competition between DN and sensory stimulus: Sensory evoked activity were attenuated in subjects with strongest DN correlation

Variation in fmri intensity in PCC and MPFC during 5 min period of watching a Fixed cross hair (Fox 2005) individual thoughts and musings? But spontaneous fluctuations also exist in numerous brain systems, are present at sleep And under deep anesthesia and are somewhat slow for cognitive events => Could also be only low level physiological processes

Broad low level focus of attention when monitoring the external world for unexpected events DN reflects continuous provision for resources for spontaneous, broad and exogenously driven information gathering State of awareness of the external environment Sentinel Hypothesis Balint s syndrome (can be induces by lesions across the precuneus and cuneus): perception only of a small portion of the visual world, disrupted global attention

Autism Spectrum Disease (ASD) dmpfc volume reduction in ASD Activity in MPFC correlated with social interaction deficit Direct study of DN activity in ASD revealed atypical dmpfc and PCC activity (Kennedy 2006)

Schizophrenia: Altered perception of reality (Liddle 1987) Impaired memory and attention (Kuperberg&Heckers 2000) Hallucinations, delusion and confusions correlated with increased DN activity (MPFC, PCC/Rsp) (Garrity 2007) Higher correlations of DN regions than in controls: overactive DN (Zhou 2007) Boundaries between imaginations and reality disrupted

Memory loss Disturbance of executive functions Resting glucose metabolism: reduced metabolism compared to controls Functional changes in the Atrophy in the medial temporal lobe

DN exciting new field of studying brain activation during resting DN information can be obtained from clinical fmri exams > potential clinical applications in neurodegenerative disease