Mapping brain function in freely moving subjects

Abstract

Expression of many fundamental mammalian behaviors such as, for example, aggression, mating, foraging or social behaviors, depend on locomotor activity. A central dilemma in the functional neuroimaging of these behaviors has been the fact that conventional neuroimaging techniques generally rely on immobilization of the subject, which extinguishes all but the simplest activity. Ideally, imaging could occur in freely moving subjects, while presenting minimal interference with the subject's natural behavior. Here we provide an overview of several approaches that have been undertaken in the past to achieve this aim in both tethered and freely moving animals, as well as in nonrestrained human subjects. Applications of specific radiotracers to single photon emission computed tomography and positron emission tomography are discussed in which brain activation is imaged after completion of the behavioral task and capture of the tracer. Potential applications to clinical neuropsychiatry are discussed, as well as challenges inherent to constraint-free functional neuroimaging. Future applications of these methods promise to increase our understanding of the neural circuits underlying mammalian behavior in health and disease.

Impact of L-DOPA treatment on regional cerebral blood flow and metabolism in the basal ganglia in a rat model of Parkinson's disease

“…The selected radiotracer was delivered intravenously through the catheter with a speed of 0.1 ml/sec. The tracer circulation time was optimized to the physiological parameters being examined, consisting of 10 seconds for [ 14 C]-IAP, 45 minutes for [ 14 C]2-DG, and 25 minutes for [ 14 C]-AIB (Blasberg et al, 1983; Holschneider and Maarek, 2004; Sakurada et al, 1978; Sokoloff et al, 1977). Following the given tracer circulation time, animals were immediately anaesthetized by a bolus injection of sodium pentobarbital (240 mg/kg; Apoteksbolaget AB) through the catheter and killed by decapitation.…”

CNS animal fMRI in pain and analgesia

“…Such methods have some advantages including the ability to evaluate behaviors in freely moving animals ((Holschneider and Maarek, 2004, 2008)). As noted in the latter reference, these approaches can now be used for to the functional brain mapping of behaviors providing three-dimensional reconstruction of the brain from autoradiographic sections and voxel-based analysis of the whole brain, and generation of maps of the flattened cortical regions.…”

Brain maps on the go: Functional imaging during motor challenge in animals

“…Euthanasia must be rapid to prevent nonspecific diffusion of the [ 14 C]-iodoantipyrine (34), and by necessity cryosectioning of the brain is required. For studies choosing to use PET/microPET or SPECT/ microSPECT to image brain function, the problem of behavioral restraint can be solved and euthanasia avoided if radiotracers are administered by non-agitating means, and regional brain activation is imaged after completion of the behavioral task and capture of the tracer (65). Since imaging of brain metabolism using a tracer such as radiolabelled 2-deoxy-D-glucose (2-DG) typically takes place after tracer uptake is complete and relatively imperturbable, this method is suitable for neuroimaging in nontethered, ambulatory subjects.…”

“…This tracer is extracted and captured intracellularly, similar to [ 18 F]-FDG but in a substantially shorter time frame (2 minutes versus 45 minutes for [ 18 F]-FDG). When labeled with 61 Cu (t 1/2 =3.3 h), 64 Cu (t 1/2 =12.7 h), or 67 Cu (t 1/2 = 58.5 h), Cu-PTSM might be appropriate for neuroimaging in freely moving subjects (65). Relevant tracers for SPECT applications include Technetium-99m-hexamethylproyleneamine oxime (Tc 99m -D,L-HMPAO or exametazime; radioactive t 1/2 =6.03 h,), a commercially available tracer (Ceretec, Nycomed-Amersham, Little Chalfont, UK) that has been used to study brain activation in freely-moving human subjects during walking (62) and during cycling on a stationary bicycle (69).…”