Band 22, Heft 6

No abstract available

We have recently developed a mobile brain imaging method (MoBI), that allows for simultaneous recording of brain and body dynamics of humans actively behaving in and interacting with their environment. A mobile imaging approach was needed to study cognitive processes that are inherently based on the use of human physical structure to obtain behavioral goals. This review gives examples of the tight coupling between human physical structure with cognitive processing and the role of supraspinal activity during control of human stance and locomotion. Existing brain imaging methods for actively behaving participants are described and new sensor technology allowing for mobile recordings of different behavioral states in humans is introduced. Finally, we review recent work demonstrating the feasibility of a MoBI system that was developed at the Swartz Center for Computational Neuroscience at the University of California, San Diego, demonstrating the range of behavior that can be investigated with this method.

In this review, we highlight the role of neuroimaging techniques in studying the emotional and cognitive-behavioral components of the addiction syndrome by focusing on the neural substrates subserving them. The phenomenology of drug addiction can be characterized by a recurrent pattern of subjective experiences that includes drug intoxication, craving, bingeing, and withdrawal with the cycle culminating in a persistent preoccupation with obtaining, consuming, and recovering from the drug. In the past two decades, imaging studies of drug addiction have demonstrated deficits in brain circuits related to reward and impulsivity. The current review focuses on studies employing positron emission tomography (PET), functional magnetic resonance imaging (fMRI), and electroencephalography (EEG) to investigate these behaviors in drug-addicted human populations. We begin with a brief account of drug addiction followed by a technical account of each of these imaging modalities. We then discuss how these techniques have uniquely contributed to a deeper understanding of addictive behaviors.

Disturbances of dopaminergic neurotransmission may be caused by changes in concentrations of synaptic dopamine (DA) and/or availabilities of pre- and post-synaptic transporter and receptor binding sites. We present a series of experiments which focus on the regulatory mechanisms of the dopamin(DA)ergic synapse in the rat striatum. In these studies, DA transporter (DAT) and/or D 2 receptor binding were assessed with either small animal single-photon emission computed tomography (SPECT) or positron emission tomography (PET) after pharmacological challenge with haloperidol, L-DOPA and methylphenidate, and after nigrostriatal 6-hydroxydopamine lesion. Investigations of DAT binding were performed with [ 123 I]N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane ([ 123 I]FP-CIT). D 2 receptor bindingd was assessed with either [ 123 I](S)-2-hydroxy-3-iodo-6-methoxy-N-[(1-ethyl-2-pyrrolidinyl)methyl]benzamide ([ 123 I]IBZM) or [ 18 F]1[3-(4′fluorobenzoyl)propyl]-4-(2-keto-3-methyl-1-benzimidazolinyl)piperidine ([ 18 F]FMB). Findings demonstrate that in vivo investigations of transporter and/or receptor binding are feasible with small animal SPECT and PET. Therefore, tracers that are radiolabeled with isotopes of comparatively long half-lives such as 123 I may be employed. Our approach to quantify DAT and/or D 2 receptor binding at baseline and after pharmacological interventions inducing DAT blockade, D 2 receptor blockade, and increases or decreases of endogenous DA concentrations holds promise for the in vivo assessment of synaptic function. This pertains to animal models of diseases associated with pre- or postsynaptic DAergic deficiencies such as Parkinson’s disease, Huntington’s disease, attention-deficit/hyperactivity disorder, schizophrenia or drug abuse.

Behavioral studies are an important part of neuroscience. They allow inferences about the functions of the brain and any internal states and processes it controls. Positron emission tomography (PET) is an in vivo imaging technique that provides insights into the mechanisms of neuronal communication. In this review, we focus on some of the contributions of PET to the field of behavioral neuroscience. Small animals typically require anesthesia to remain still during PET imaging, which places a burden on behavioral studies. Our approach integrates PET with behavioral observations using a miniature PET scanner that rats wear on the head, a mobility system to facilitate animal movement and ways to integrate the PET data with behavioral measures. We summarize our studies that assessed spontaneous, self-initiated behavioral activity and dopamine D2 receptor functions simultaneously.

Medical researchers have used structural and functional imaging techniques to study various neurological phenomena. Humans are typically conscious for both structural and functional neuroimaging studies. The use of functional neuro­imaging techniques in mouse-based animal models is typically accomplished with restrained or anesthetized mice. A system was developed to perform functional imaging with single-photon emission computed tomography of awake mice to avoid the confounding influences of anesthesia or physical restraint. This review article provides an overview of the technique and how it is presently being used. The system is designed for brain imaging and uses infrared reflectors to track the head position as a function of time. The detected photons are acquired in list mode and are time-stamped. The position of the rotating gamma camera is also recorded as a function of time. These three sets of data are integrated together in an iterative image reconstruction program that performs motion compensation. The successful performance of the system is demonstrated in moving phantom and awake animal studies. The system and methodology has the potential of being a powerful tool in behavioral neuroimaging studies involving awake, unrestrained mice.

Awake animal imaging is becoming an important tool in behavioral neuroscience and preclinical drug discovery. Non-invasive ultra-high-field, functional magnetic resonance imaging (fMRI) provides a window to the mind, making it possible to image changes in brain activity across distributed, integrated neural circuits with high temporal and spatial reso­lution. In theory, changes in brain function, anatomy, and chemistry can be recorded in the same animal from early life into old age under stable or changing environmental conditions. This prospective capability of animal imaging to follow changes in brain neurobiology after genetic or environmental insult has great value to the fields of psychiatry and neurology and probably stands as the key advantage of MRI over other methods in the neuroscience toolbox. In addition, awake animal imaging offers the ability to record signal changes across the entire brain in seconds. When combined with the use of 3D segmented, annotated, brain atlases, and computational analysis, it is possible to reconstruct distributed, integrated neural circuits or ‘fingerprints’ of brain activity. These fingerprints can be used to characterize the activity and function of new psychotherapeutics in preclinical development and to study the neurobiology of integrated neural circuits controlling cognition and emotion. In this review, we describe the methods used to image awake animals and the recent advances in the radiofrequency electronics, pulse sequences, and the development of 3D segmented atlases and software for image analysis. Results from pharmacological MRI studies and from studies using provocation paradigms to elicit emotional responses are provided as a small sample of the number of different applications possible with awake animal imaging.

Manganese ion (Mn 2+ ) is a calcium (Ca 2+ ) analog that can enter neurons and other excitable cells through voltage gated Ca 2+ channels. Mn 2+ is also a paramagnetic that shortens the spin-lattice relaxation time constant (T 1 ) of tissues where it has accumulated, resulting in positive contrast enhancement. Mn 2+ was first investigated as a magnetic resonance imaging (MRI) contrast agent approximately 20 years ago to assess the toxicity of the metal in rats. In the late 1990s, Alan Koretsky and colleagues pioneered the use of manganese enhanced MRI (MEMRI) towards studying brain activity, tract tracing and enhancing anatomical detail. This review will describe the methodologies and applications of MEMRI in the following areas: monitoring brain activity in animal models, in vivo neuronal tract tracing and using MEMRI to assess in vivo axonal transport rates.

It is known that a remaining challenge for functional brain imaging is to distinguish the coupling and decoupling effects among neuronal activity, cerebral metabolism, and vascular hemodynamics, which highlights the need for new tools to enable simultaneous measures of these three properties in vivo . Here, we review current neuroimaging techniques and their prospects and potential limitations for tackling this challenge. We then report a novel dual-wavelength laser speckle imaging (DW-LSI) tool developed in our labs that enables simultaneous imaging of cerebral blood flow (CBF), cerebral blood volume, and tissue hemoglobin oxygenation, which allows us to monitor neurovascular and tissue metabolic activities at high spatiotemporal resolutions over a relatively large field of view. Moreover, we report digital frequency ramping Doppler optical coherence tomography (DFR-OCT) that allows for quantitative 3D imaging of the CBF network in vivo . In parallel, we review calcium imaging techniques to track neuronal activity, including intracellular calcium approach using Rhod2 fluorescence technique that we develop to detect neuronal activity in vivo . We report a new multimodality imaging platform that combines DW-LSI, DFR-OCT, and calcium fluorescence imaging for simultaneous detection of cortical hemodynamics, cerebral metabolism, and neuronal activities of the animal brain in vivo , as well as its integration with microprobes for imaging neuronal function in deep brain regions in vivo . Promising results of in vivo animal brain functional studies suggest the potential of this multimodality approach for future awake animal and behavioral studies.