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1.
NMR Biomed ; 36(8): e4928, 2023 08.
Article in English | MEDLINE | ID: mdl-36939270

ABSTRACT

Infants and toddlers are a challenging population upon which to perform magnetic resonance imaging (MRI) of the brain, both in research and clinical settings. Because of the large range in head size during the early years of development, paediatric neuro-MRI requires a radiofrequency (RF) coil, or set of coils, that is tailored to head size to provide the highest image quality. Mitigating techniques must also be employed to reduce and correct for subject motion. This manuscript describes an RF coil with a tailored mechanical-electrical design that can adapt to the head size of 3-month-old infants to 3-year-old toddlers. The RF coil was designed with tight-fitting coil elements to improve the signal-to-noise ratio (SNR) in comparison with commercially available adult head coils, while simultaneously aiding in immobilization. The coil was designed without visual obstruction to facilitate an unimpeded view of the child's face and the potential application of camera or motion-tracking systems. Despite the lack of elements over the face, the paediatric coil produced higher SNR over most of the brain compared with adult coils, including more than twofold in the periphery. Acceleration rates of fourfold in each Cartesian direction could be achieved. High SNR allowed for short acquisition times through accelerated imaging protocols and reduced the probability of motion during a scan. Modification of the acquisition protocol, with immobilization of the head through the adjustable coil geometry, and subsequently being combined with a motion-tracking system, provides a compelling platform for scanning paediatric populations without sedation and with improved image quality.


Subject(s)
Brain , Magnetic Resonance Imaging , Adult , Humans , Child, Preschool , Infant , Child , Magnetic Resonance Imaging/methods , Signal-To-Noise Ratio , Brain/diagnostic imaging , Phantoms, Imaging , Radio Waves , Equipment Design
2.
Neuroimage ; 252: 119030, 2022 05 15.
Article in English | MEDLINE | ID: mdl-35217206

ABSTRACT

The common marmoset (Callithrix jacchus) is quickly gaining traction as a premier neuroscientific model. However, considerable progress is still needed in understanding the functional and structural organization of the marmoset brain to rival that documented in longstanding preclinical model species, like mice, rats, and Old World primates. To accelerate such progress, we present the Marmoset Functional Brain Connectivity Resource (marmosetbrainconnectome.org), currently consisting of over 70 h of resting-state fMRI (RS-fMRI) data acquired at 500 µm isotropic resolution from 31 fully awake marmosets in a common stereotactic space. Three-dimensional functional connectivity (FC) maps for every cortical and subcortical gray matter voxel are stored online. Users can instantaneously view, manipulate, and download any whole-brain functional connectivity (FC) topology (at the subject- or group-level) along with the raw datasets and preprocessing code. Importantly, researchers can use this resource to test hypotheses about FC directly - with no additional analyses required - yielding whole-brain correlations for any gray matter voxel on demand. We demonstrate the resource's utility for presurgical planning and comparison with tracer-based neuronal connectivity as proof of concept. Complementing existing structural connectivity resources for the marmoset brain, the Marmoset Functional Brain Connectivity Resource affords users the distinct advantage of exploring the connectivity of any voxel in the marmoset brain, not limited to injection sites nor constrained by regional atlases. With the entire raw database (RS-fMRI and structural images) and preprocessing code openly available for download and use, we expect this resource to be broadly valuable to test novel hypotheses about the functional organization of the marmoset brain.


Subject(s)
Callithrix , Wakefulness , Access to Information , Animals , Brain/physiology , Callithrix/physiology , Humans , Magnetic Resonance Imaging/methods , Mice , Rats
3.
Magn Reson Med ; 87(5): 2551-2565, 2022 05.
Article in English | MEDLINE | ID: mdl-34932225

ABSTRACT

PURPOSE: To develop an RF coil with an integrated commercial field camera for ultrahigh field (7T) neuroimaging. The RF coil would operate within a head-only gradient coil and be subject to the corresponding design constraints. The RF coil can thereafter be used for subject-specific correction of k-space trajectories-notably in gradient-sensitive sequences such as single-shot spiral imaging. METHODS: The transmit and receive performance was evaluated before and after the integration of field probes, whereas field probes were evaluated when in an optimal configuration external to the coil and after their integration. Diffusion-weighted EPI and single-shot spiral acquisitions were employed to evaluate the efficacy of correcting higher order field perturbations and the consequent effect on image quality. RESULTS: Field probes had a negligible effect on RF-coil performance, including the transmit efficiency, transmit uniformity, and mean SNR over the brain. Modest reductions in field-probe signal lifetimes were observed, caused primarily by nonidealities in the gradient and shim fields of the head-only gradient coil at the probe positions. The field-monitoring system could correct up to second-order field perturbations in single-shot spiral imaging. CONCLUSION: The integrated RF coil and field camera was capable of concurrent-field monitoring within a 7T head-only scanner and facilitated the subsequent correction of k-space trajectories during spiral imaging.


Subject(s)
Magnetic Resonance Imaging , Radio Waves , Brain/diagnostic imaging , Equipment Design , Magnetic Resonance Imaging/methods , Neuroimaging/methods , Phantoms, Imaging
4.
Nat Commun ; 12(1): 6608, 2021 11 16.
Article in English | MEDLINE | ID: mdl-34785685

ABSTRACT

Social cognition is a dynamic process that requires the perception and integration of a complex set of idiosyncratic features between interacting conspecifics. Here we present a method for simultaneously measuring the whole-brain activation of two socially interacting marmoset monkeys using functional magnetic resonance imaging. MRI hardware (a radiofrequency coil and peripheral devices) and image-processing pipelines were developed to assess brain responses to socialization, both on an intra-brain and inter-brain level. Notably, the brain activation of a marmoset when viewing a second marmoset in-person versus when viewing a pre-recorded video of the same marmoset-i.e., when either capable or incapable of socially interacting with a visible conspecific-demonstrates increased activation in the face-patch network. This method enables a wide range of possibilities for potentially studying social function and dysfunction in a non-human primate model.


Subject(s)
Brain/physiology , Callithrix/physiology , Magnetic Resonance Imaging/methods , Wakefulness , Animals , Brain/diagnostic imaging , Brain Mapping , Cognitive Neuroscience , Face , Female , Humans , Image Processing, Computer-Assisted , Magnetic Resonance Imaging/instrumentation , Male
5.
Neuroimage ; 227: 117631, 2021 02 15.
Article in English | MEDLINE | ID: mdl-33316391

ABSTRACT

High-resolution functional MRI studies have become a powerful tool to non-invasively probe the sub-millimeter functional organization of the human cortex. Advances in MR hardware, imaging techniques and sophisticated post-processing methods have allowed high resolution fMRI to be used in both the clinical and academic neurosciences. However, consensus within the community regarding the use of gradient echo (GE) or spin echo (SE) based acquisition remains largely divided. On one hand, GE provides a high temporal signal-to-noise ratio (tSNR) technique sensitive to both the macro- and micro-vascular signal while SE based methods are more specific to microvasculature but suffer from lower tSNR and specific absorption rate limitations, especially at high field and with short repetition times. Fortunately, the phase of the GE-EPI signal is sensitive to vessel size and this provides a potential avenue to reduce the macrovascular weighting of the signal (phase regression, Menon 2002). In order to determine the efficacy of this technique at high-resolution, phase regression was applied to GE-EPI timeseries and compared to SE-EPI to determine if GE-EPI's specificity to the microvascular compartment improved. To do this, functional data was collected from seven subjects on a neuro-optimized 7 T system at 800 µm isotropic resolution with both GE-EPI and SE-EPI while observing an 8 Hz contrast reversing checkerboard. Phase data from the GE-EPI was used to create a microvasculature-weighted time series (GE-EPI-PR). Anatomical imaging (MP2RAGE) was also collected to allow for surface segmentation so that the functional results could be projected onto a surface. A multi-echo gradient echo sequence was collected and used to identify venous vasculature. The GE-EPI-PR surface activation maps showed a high qualitative similarity with SE-EPI and also produced laminar activity profiles similar to SE-EPI. When the GE-EPI and GE-EPI-PR distributions were compared to SE-EPI it was shown that GE-EPI-PR had similar distribution characteristics to SE-EPI (p < 0.05) across the top 60% of cortex. Furthermore, it was shown that GE-EPI-PR has a higher contrast-to-noise ratio (0.5 ± 0.2, mean ± std. dev. across layers) than SE-EPI (0.27 ± 0.07) demonstrating the technique has higher sensitivity than SE-EPI. Taken together this evidence suggests phase regression is a useful method in low SNR studies such as high-resolution fMRI.


Subject(s)
Magnetic Resonance Imaging/methods , Visual Cortex/diagnostic imaging , Adult , Brain Mapping/methods , Echo-Planar Imaging/methods , Female , Humans , Image Processing, Computer-Assisted/methods , Male , Signal-To-Noise Ratio , Young Adult
6.
NMR Biomed ; 34(3): e4457, 2021 03.
Article in English | MEDLINE | ID: mdl-33305466

ABSTRACT

Many neuroscience applications have adopted functional MRI as a tool to investigate the healthy and diseased brain during the completion of a task. While ultra-high-field MRI has allowed for improved contrast and signal-to-noise ratios during functional MRI studies, it remains a challenge to create local radiofrequency coils that can accommodate an unobstructed visual field and be suitable for routine use, while at the same time not compromise performance. Performance (both during transmission and reception) can be improved by using close-fitting coils; however, maintaining sensitivity over the whole brain often requires the introduction of coil elements proximal to the eyes, thereby partially occluding the subject's visual field. This study presents a 7 T head coil, with eight transmit dipoles and 32 receive loops, that is designed to remove visual obstructions from the subject's line of sight, allowing for an unencumbered view of visual stimuli, the reduction of anxiety induced from small enclosures, and the potential for eye-tracking measurements. The coil provides a practical solution for routine imaging, including a split design (anterior and posterior halves) that facilitates subject positioning, including those with impaired mobility, and the placement of devices required for patient comfort and motion reduction. The transmit and receive coils displayed no degradation of performance due to adaptions to the design topology (both mechanical and electrical) required to create an unobstructed visual field. All computer-aided design files, electromagnetic simulation models, transmit field maps and local specific absorption rate matrices are provided to promote reproduction.


Subject(s)
Radio Waves , Visual Fields/physiology , Computer Simulation , Head , Humans , Phantoms, Imaging , Signal-To-Noise Ratio , Spin Labels
7.
Eur Arch Psychiatry Clin Neurosci ; 271(1): 3-15, 2021 Feb.
Article in English | MEDLINE | ID: mdl-32683527

ABSTRACT

Repetitive transcranial magnetic stimulation (rTMS), when applied to left dorsolateral prefrontal cortex (LDLPFC), reduces negative symptoms of schizophrenia, but has no effect on positive symptoms. In a small number of cases, it appears to worsen the severity of positive symptoms. It has been hypothesized that high-frequency rTMS of the LDLPFC might increase the dopaminergic neurotransmission by driving the activity of the left striatum in the basal ganglia (LSTR)-increasing striatal dopaminergic activity. This hypothesis relies on the assumption that either the frontal-striatal connection or the intrinsic frontal and/or striatal connections covary with the severity of positive symptoms. The current work aimed to evaluate this assumption by studying the association between positive and negative symptoms severity and the effective connectivity within the frontal and striatal network using dynamic causal modeling of resting state fMRI in a sample of 19 first episode psychosis subjects. We found that the total score of positive symptoms of schizophrenia is strongly associated with the frontostriatal circuitry. Stronger intrinsic inhibitory tone of LDLPFC and LSTR, as well as decreased bidirectional excitatory influence between the LDLPFC and the LSTR is related to the severity of positive symptoms, especially delusions. We interpret that an increase in striatal dopaminergic tone that underlies positive symptoms is likely associated with increased prefrontal inhibitory tone, strengthening the frontostriatal 'brake'. Furthermore, based on our model, we propose that lessening of positive symptoms could be achieved by means of continuous theta-burst or low-frequency (1 Hz) rTMS of the prefrontal area.


Subject(s)
Neostriatum/physiopathology , Prefrontal Cortex/physiopathology , Schizophrenia/physiopathology , Schizophrenia/therapy , Transcranial Magnetic Stimulation , Adolescent , Adult , Dopamine/metabolism , Dorsolateral Prefrontal Cortex/physiopathology , Female , Humans , Magnetic Resonance Imaging , Male , Young Adult
8.
J Neurophysiol ; 124(6): 1900-1913, 2020 12 01.
Article in English | MEDLINE | ID: mdl-33112698

ABSTRACT

The common marmoset (Callithrix jacchus) is a small-bodied New World primate that is becoming an important model to study brain functions. Despite several studies exploring the somatosensory system of marmosets, all results have come from anesthetized animals using invasive techniques and postmortem analyses. Here, we demonstrate the feasibility for getting high-quality and reproducible somatosensory mapping in awake marmosets with functional magnetic resonance imaging (fMRI). We acquired fMRI sequences in four animals, while they received tactile stimulation (via air-puffs), delivered to the face, arm, or leg. We found a topographic body representation with the leg representation in the most medial part, the face representation in the most lateral part, and the arm representation between leg and face representation within areas 3a, 3b, and 1/2. A similar sequence from leg to face from caudal to rostral sites was identified in areas S2 and PV. By generating functional connectivity maps of seeds defined in the primary and second somatosensory regions, we identified two clusters of tactile representation within the posterior and midcingulate cortex. However, unlike humans and macaques, no clear somatotopic maps were observed. At the subcortical level, we found a somatotopic body representation in the thalamus and, for the first time in marmosets, in the putamen. These maps have similar organizations, as those previously found in Old World macaque monkeys and humans, suggesting that these subcortical somatotopic organizations were already established before Old and New World primates diverged. Our results show the first whole brain mapping of somatosensory responses acquired in a noninvasive way in awake marmosets.NEW & NOTEWORTHY We used somatosensory stimulation combined with functional MRI (fMRI) in awake marmosets to reveal the topographic body representation in areas S1, S2, thalamus, and putamen. We showed the existence of a body representation organization within the thalamus and the cingulate cortex by computing functional connectivity maps from seeds defined in S1/S2, using resting-state fMRI data. This noninvasive approach will be essential for chronic studies by guiding invasive recording and manipulation techniques.


Subject(s)
Brain Mapping , Gyrus Cinguli/physiology , Putamen/physiology , Somatosensory Cortex/physiology , Thalamus/physiology , Touch Perception/physiology , Animals , Arm , Behavior, Animal/physiology , Callithrix , Connectome , Face , Female , Gyrus Cinguli/diagnostic imaging , Leg , Magnetic Resonance Imaging , Male , Physical Stimulation , Putamen/diagnostic imaging , Somatosensory Cortex/diagnostic imaging , Thalamus/diagnostic imaging
9.
J Neurosci ; 40(48): 9236-9249, 2020 11 25.
Article in English | MEDLINE | ID: mdl-33097633

ABSTRACT

Understanding the similarity of cortico-subcortical networks topologies between humans and nonhuman primate species is critical to study the origin of network alternations underlying human neurologic and neuropsychiatric diseases. The New World common marmoset (Callithrix jacchus) has become popular as a nonhuman primate model for human brain function. Most marmoset connectomic research, however, has exclusively focused on cortical areas, with connectivity to subcortical networks less extensively explored. Here, we aimed to first isolate patterns of subcortical connectivity with cortical resting-state networks in awake marmosets using resting-state fMRI, then to compare these networks with those in humans using connectivity fingerprinting. In this study, we used 5 marmosets (4 males, 1 female). While we could match several marmoset and human resting-state networks based on their functional fingerprints, we also found a few striking differences, for example, strong functional connectivity of the default mode network with the superior colliculus in marmosets that was much weaker in humans. Together, these findings demonstrate that many of the core cortico-subcortical networks in humans are also present in marmosets, but that small, potentially functionally relevant differences exist.SIGNIFICANCE STATEMENT The common marmoset is becoming increasingly popular as an additional preclinical nonhuman primate model for human brain function. Here we compared the functional organization of cortico-subcortical networks in marmosets and humans using ultra-high field fMRI. We isolated the patterns of subcortical connectivity with cortical resting-state networks (RSNs) in awake marmosets using resting-state fMRI and then compared these networks with those in humans using connectivity fingerprinting. While we could match several marmoset and human RSNs based on their functional fingerprints, we also found several striking differences. Together, these findings demonstrate that many of the core cortico-subcortical RSNs in humans are also present in marmosets, but that small, potentially functionally relevant differences exist.


Subject(s)
Cerebral Cortex/physiology , Neural Pathways/physiology , Animals , Callithrix , Cerebral Cortex/diagnostic imaging , Connectome , Female , Humans , Magnetic Resonance Imaging , Male , Neural Pathways/diagnostic imaging , Rest/physiology , Species Specificity , Superior Colliculi/physiology
10.
Proc Natl Acad Sci U S A ; 117(35): 21681-21689, 2020 09 01.
Article in English | MEDLINE | ID: mdl-32817555

ABSTRACT

With the medial frontal cortex (MFC) centrally implicated in several major neuropsychiatric disorders, it is critical to understand the extent to which MFC organization is comparable between humans and animals commonly used in preclinical research (namely rodents and nonhuman primates). Although the cytoarchitectonic structure of the rodent MFC has mostly been conserved in humans, it is a long-standing question whether the structural analogies translate to functional analogies. Here, we probed this question using ultra high field fMRI data to compare rat, marmoset, and human MFC functional connectivity. First, we applied hierarchical clustering to intrinsically define the functional boundaries of the MFC in all three species, independent of cytoarchitectonic definitions. Then, we mapped the functional connectivity "fingerprints" of these regions with a number of different brain areas. Because rats do not share cytoarchitectonically defined regions of the lateral frontal cortex (LFC) with primates, the fingerprinting method also afforded the unique ability to compare the rat MFC and marmoset LFC, which have often been suggested to be functional analogs. The results demonstrated remarkably similar intrinsic functional organization of the MFC across the species, but clear differences between rodent and primate MFC whole-brain connectivity. Rat MFC patterns of connectivity showed greatest similarity with premotor regions in the marmoset, rather than dorsolateral prefrontal regions, which are often suggested to be functionally comparable. These results corroborate the viability of the marmoset as a preclinical model of human MFC dysfunction, and suggest divergence of functional connectivity between rats and primates in both the MFC and LFC.


Subject(s)
Neural Pathways/physiology , Prefrontal Cortex/physiology , Animals , Biological Evolution , Brain/physiology , Brain Mapping/methods , Callithrix/anatomy & histology , Connectome/methods , Female , Frontal Lobe/anatomy & histology , Frontal Lobe/physiology , Gray Matter/physiology , Humans , Magnetic Resonance Imaging/methods , Male , Neural Pathways/anatomy & histology , Prefrontal Cortex/anatomy & histology , Rats , Rats, Wistar
11.
NMR Biomed ; 33(11): e4387, 2020 11.
Article in English | MEDLINE | ID: mdl-32749022

ABSTRACT

The magnetization-prepared two-rapid-gradient-echo (MP2RAGE) sequence is used for structural T1 -weighted imaging and T1 mapping of the human brain. In this sequence, adiabatic inversion RF pulses are commonly used, which require the B1+ magnitude to be above a certain threshold. Achieving this threshold in the whole brain may not be possible at ultra-high fields because of the short RF wavelength. This results in low-inversion regions especially in the inferior brain (eg cerebellum and temporal lobes), which is reflected as regions of bright signal in MP2RAGE images. This study aims at eliminating the low-inversion-efficiency induced artifacts in MP2RAGE images at 7 T. The proposed technique takes advantage of parallel RF transmission systems by splitting the brain into two overlapping slabs and calculating the complex weights of transmit channels (ie RF shims) on these slabs for excitation and inversion independently. RF shims were calculated using fast methods implemented in the standard workflow. The excitation RF pulse was designed to obtain slabs with flat plateaus and sharp edges. These slabs were joined into a single volume during the online image reconstruction. The two-slab strategy naturally results in a signal-to-noise ratio loss; however, it allowed the use of independent shims to make the B1+ field exceed the adiabatic threshold in the inferior brain, eliminating regions of low inversion efficiency. Accordingly, the normalized root-mean-square errors in the inversion were reduced to below 2%. The two-slab strategy was found to outperform subject-specific kT -point inversion RF pulses in terms of inversion error. The proposed strategy is a simple yet effective method to eliminate low-inversion-efficiency artifacts; consequently, MP2RAGE-based, artifact-free T1 -weighted structural images were obtained in the whole brain at 7 T.


Subject(s)
Algorithms , Artifacts , Brain/diagnostic imaging , Magnetic Resonance Imaging , Radio Waves , Contrast Media/chemistry , Humans
12.
Cereb Cortex ; 30(11): 5943-5959, 2020 10 01.
Article in English | MEDLINE | ID: mdl-32556184

ABSTRACT

The common marmoset (Callithrix jacchus) is a New World primate that is becoming increasingly popular as a preclinical model. To assess functional connectivity (FC) across the marmoset brain, resting-state functional MRI (RS-fMRI) is often performed under isoflurane anesthesia to avoid the effects of motion, physiological stress, and training requirements. In marmosets, however, it remains unclear how isoflurane anesthesia affects patterns of FC. Here, we investigated the effects of isoflurane on FC when delivered with either medical air or 100% pure oxygen, two canonical methods of inhalant isoflurane anesthesia delivery. The results demonstrated that when delivered with either medical air or 100% oxygen, isoflurane globally decreased FC across resting-state networks that were identified in awake marmosets. Generally, although isoflurane globally decreased FC in resting-state networks, the spatial structure of the networks was preserved. Outside of the context of RS networks, we indexed pair-wise functional connectivity between regions across the brain and found that isoflurane substantially altered interhemispheric and thalamic FC. Taken together, these findings indicate that RS-fMRI under isoflurane anesthesia is useful to evaluate the global structure of functional networks, but may obfuscate important nodes of some network components when compared to data acquired in fully awake marmosets.


Subject(s)
Anesthetics, Inhalation/pharmacology , Brain/drug effects , Isoflurane/pharmacology , Neural Pathways/drug effects , Rest , Wakefulness , Animals , Brain/physiology , Callithrix , Female , Magnetic Resonance Imaging , Male , Neural Pathways/physiology , Rest/physiology , Wakefulness/physiology
13.
Neuroimage ; 215: 116815, 2020 07 15.
Article in English | MEDLINE | ID: mdl-32278898

ABSTRACT

An object that is looming toward a subject or receding away contains important information for determining if this object is dangerous, beneficial or harmless. This information (motion, direction, identity, time-to-collision, size, velocity) is analyzed by the brain in order to execute the appropriate behavioral responses depending on the context: fleeing, freezing, grasping, eating, exploring. In the current study, we performed ultra-high-field functional MRI (fMRI) at 9.4T in awake marmosets to explore the patterns of brain activation elicited by visual stimuli looming toward or receding away from the monkey. We found that looming and receding visual stimuli activated a large cortical network in frontal, parietal, temporal and occipital cortex in areas involved in the analysis of motion, shape, identity and features of the objects. Looming stimuli strongly activated a network composed of portions of the pulvinar, superior colliculus, putamen, parietal, prefrontal and temporal cortical areas. These activations suggest the existence of a network that processes visual stimuli looming toward peripersonal space to predict the consequence of these stimuli. Together with previous studies in macaque monkeys, these findings indicate that this network is preserved across Old and New World primates.


Subject(s)
Brain/physiology , Form Perception/physiology , Magnetic Resonance Imaging/methods , Motion Perception/physiology , Visual Pathways/physiology , Wakefulness/physiology , Animals , Brain/diagnostic imaging , Callithrix , Male , Photic Stimulation/methods , Reaction Time/physiology , Visual Pathways/diagnostic imaging
14.
Biomed Phys Eng Express ; 6(4): 045022, 2020 07 07.
Article in English | MEDLINE | ID: mdl-33444282

ABSTRACT

A gradient coil with integrated second and third order shims has been designed and constructed for use inside an actively shielded 310 mm horizontal bore 9.4 T small animal MRI. An extension of the boundary element method, to minimise the power deposited in conducting surfaces, was used to design the gradients, and a boundary element method with a constraint on mutual inductance was used to design the shims. The gradient coil allows for improved imaging performance and was optimized for an imaging region appropriate for marmoset imaging studies. Efficiencies of 1.5 mT m-1 A-1 were achieved in a 15 cm wide bore while maintaining gradient uniformity ≤5% over the 8 cm region of interest. Two new cooling methods were implemented which allowed the gradient coil to operate at 100 A RMS, 25 % of max current with a temperature rise below 30 C.


Subject(s)
Brain/diagnostic imaging , Callithrix/physiology , Magnetic Resonance Imaging/instrumentation , Magnetic Resonance Imaging/methods , Algorithms , Animals , Equipment Design , Magnetics , Temperature
15.
Neuroimage ; 204: 116241, 2020 01 01.
Article in English | MEDLINE | ID: mdl-31586676

ABSTRACT

Resting-state functional MRI (RS-fMRI) is widely used to assess how strongly different brain areas are connected. However, this connection obtained by RS-fMRI, which is called functional connectivity (FC), simply refers to the correlation of blood oxygen level-dependent (BOLD) signals across time it has yet to be quantified how accurately FC reflects cellular connectivity (CC). In this study, we elucidated this relationship using RS-fMRI and quantitative tracer data in marmosets. In addition, we also elucidated the effects of distance between two brain regions on the relationship between FC and CC across seed region. To calculate FC, we used full correlation approach that is considered to reflect not only direct (monosynaptic connections) but also indirect pathways (polysynaptic connections). Our main findings are that: (1) overall FC obtained by RS-fMRI was highly correlated with tracer-based CC, but correlation coefficients varied remarkably across seed regions; (2) the strength of FC decreased with increase in the distance between two regions; (3) correlation coefficients between FC and CC after regressing out the effects of the distance between two regions still varied across seed regions, but some regions have strong correlations. These findings suggest that although FC reflects the strength of monosynaptic pathways, it is strongly affected by the distance between regions.


Subject(s)
Brain , Connectome , Nerve Net , Neuroanatomical Tract-Tracing Techniques , Animals , Brain/anatomy & histology , Brain/diagnostic imaging , Brain/physiology , Callithrix , Female , Magnetic Resonance Imaging , Male , Nerve Net/anatomy & histology , Nerve Net/diagnostic imaging , Nerve Net/physiology
16.
Neuroimage ; 202: 116147, 2019 11 15.
Article in English | MEDLINE | ID: mdl-31479755

ABSTRACT

Saccadic tasks are often used to index aberrations of cognitive function in patient populations, with several neuropsychiatric and neurologic disorders characterized by saccadic dysfunction. The common marmoset (Callithrix jacchus) has received recent attention as an additional primate model for studying the neural basis of these dysfunctions - marmosets are amenable to a host of genetic manipulation techniques and have a lissencephalic cortex, which is well suited for a variety of recording techniques (e.g., calcium imaging, laminar electrophysiology). Because the marmoset cortex is mostly lissencephalic, however, the locations of frontal saccade-related regions (e.g., frontal eye fields (FEF)) are less readily identified than in Old World macaque monkeys. Further, although high quality histology-based atlases do exist for marmosets, identifying these regions based on histology alone is not always accurate, with the cytoarchitectonic boundaries often inconsonant with functional boundaries. As such, there is a need to map the functional location of these regions directly. Task-based functional magnetic resonance imaging (fMRI) is of utility in this regard, allowing for detection of whole-brain signal changes in response to moving stimuli. Here, we conducted task-based fMRI in marmosets at ultra-high field (9.4 T) during a free-viewing visuo-saccadic task. We also conducted the same task in humans at ultra-high field (7 T) to validate that our simple task was indeed evoking the visuo-saccadic circuitry we expected (as defined by a meta-analysis of fMRI saccade studies). In the marmosets, we found that the task evoked a robust visuo-saccadic topology, with visual cortex (V1, V2, V3, V4) activation extending ventrally to MT, MST, FST and dorsally into V6, 19M, 23V. This topology also included putative cingulate eye field (area 32 and 24d), posterior parietal cortex (with strongest activation in lateral intraparietal area (LIP)), and a frontolateral peak in area 8 aV in marmosets, extending into 45, 46, 8aD, 6DR, 8c, 6 aV, 6DC. Overall, these results support the view that marmosets are a promising preclinical modelling species for studying saccadic dysfunction related to neuropsychiatric or neurodegenerative human brain diseases.


Subject(s)
Callithrix/physiology , Callithrix/psychology , Frontal Lobe/physiology , Psychomotor Performance/physiology , Saccades/physiology , Visual Cortex/physiology , Adult , Animals , Brain Mapping , Eye Movement Measurements , Humans , Magnetic Resonance Imaging , Male , Neural Pathways/physiology , Species Specificity
17.
Neuroimage ; 193: 126-138, 2019 06.
Article in English | MEDLINE | ID: mdl-30879997

ABSTRACT

Marmosets are small New World primates that are posited to become an important preclinical animal model for studying intractable human brain diseases. A critical step in the development of marmosets as a viable model for human brain dysfunction is to characterize brain networks that are homologous with human network topologies. In this regard, the use of functional magnetic resonance imaging (fMRI) holds tremendous potential for functional brain mapping in marmosets. Although possible, implementation of hardware for fMRI in awake marmosets (free of the confounding effects of anesthesia) is not trivial due to the technical challenges associated with developing specialized imaging hardware. Here, we describe the design and implementation of a marmoset holder and head-fixation system with an integrated receive coil for awake marmoset fMRI. This design minimized head motion, with less than 100  µm of translation and 0.5 degrees of rotation over 15 consecutive resting state fMRI runs (at 15 min each) across 3 different marmosets. The fMRI data was of sufficient quality to reliably extract 8 resting state networks from each animal with only 60-90 min of resting state fMRI acquisition per animal. The restraint system proved to be an efficient and practical solution for securing an awake marmoset and positioning a receive array within minutes, limiting stress to the animal. This design is also amenable for multimodal imaging, allowing for electrode or lens placement above the skull via the open chamber design. All computer-aided-design (CAD) files and engineering drawings are provided as an open resource, with the majority of the parts designed to be 3D printed.


Subject(s)
Artifacts , Magnetic Resonance Imaging/instrumentation , Motion , Neuroimaging/instrumentation , Wakefulness , Animals , Callithrix , Computer-Aided Design , Equipment Design , Male
18.
Neuroimage ; 191: 81-92, 2019 05 01.
Article in English | MEDLINE | ID: mdl-30739059

ABSTRACT

Reconstructing the anatomical pathways of the brain to study the human connectome has become an important endeavour for understanding brain function and dynamics. Reconstruction of the cortico-cortical connectivity matrix in vivo often relies on noninvasive diffusion-weighted imaging (DWI) techniques but the extent to which they can accurately represent the topological characteristics of structural connectomes remains unknown. We addressed this question by constructing connectomes using DWI data collected from macaque monkeys in vivo and with data from published invasive tracer studies. We found the strength of fiber tracts was well estimated from DWI and topological properties like degree and modularity were captured by tractography-based connectomes. Rich-club/core-periphery type architecture could also be detected but the classification of hubs using betweenness centrality, participation coefficient and core-periphery identification techniques was inaccurate. Our findings indicate that certain aspects of cortical topology can be faithfully represented in noninvasively-obtained connectomes while other network analytic measures warrant cautionary interpretations.


Subject(s)
Cerebral Cortex/anatomy & histology , Connectome/methods , Diffusion Tensor Imaging/methods , Neural Pathways/anatomy & histology , Animals , Macaca mulatta
19.
J Cereb Blood Flow Metab ; 39(7): 1204-1214, 2019 07.
Article in English | MEDLINE | ID: mdl-29513623

ABSTRACT

The larger intracranial conduit vessels contribute to the total cerebral vascular resistance, and understanding their vasoreactivity to physiological stimuli is required when attempting to understand regional brain perfusion. Reactivity of the larger cerebral conduit arteries remains understudied due to a need for improved imaging methods to simultaneously assess these vessels in a single stimulus. We characterized reactivity of basal intracranial conduit arteries (basilar, right and left posterior, middle and anterior cerebral arteries) and the right and left internal carotid arteries, to manipulations in end-tidal CO2 (PetCO2). Cross-sectional area changes (%CSA) were evaluated from high-resolution (0.5 mm isotropic) images collected at 7 T using a T1-weighted 3D SPACE pulse sequence, providing high contrast between vessel lumen and surrounding tissue. Cerebrovascular reactivity was calculated as %CSA/ΔPetCO2 in eight healthy individuals (18-23 years) during normocapnia (41 ± 4 mmHg), hypercapnia (48 ± 4 mmHg; breathing 5% CO2, balance oxygen), and hypocapnia (31 ± 8 mmHg; via hyperventilation). Reactivity to hypercapnia ranged from 0.8%/mmHg in the right internal carotid artery to 2.7%/mmHg in the left anterior cerebral artery. During hypocapnia, vasoconstriction ranged from 0.9%/mmHg in the basilar artery to 2.6%/mmHg in the right posterior cerebral artery. Heterogeneous cerebrovascular reactivity to hypercapnia and hypocapnia was characterized across basal intracranial conduit and internal carotid arteries.


Subject(s)
Brain/blood supply , Cerebral Arteries/diagnostic imaging , Cerebral Arteries/physiology , Magnetic Resonance Imaging , Adolescent , Blood Flow Velocity/physiology , Carbon Dioxide/blood , Carotid Arteries/diagnostic imaging , Carotid Arteries/physiology , Female , Hemodynamics/physiology , Humans , Hypercapnia , Hypocapnia , Male , Vascular Resistance/physiology , Vasoconstriction , Young Adult
20.
J Neurosci Methods ; 312: 65-72, 2019 01 15.
Article in English | MEDLINE | ID: mdl-30468825

ABSTRACT

BACKGROUND: Small-animal MRI is an important investigative tool for basic and preclinical research. High-resolution anatomical and functional studies of the brain require artifact-free images that are acquired with a highly sensitive radiofrequency (RF) coil. NEW METHOD: The animal holder plays an important role in mitigating image artifacts: motion artifacts are reduced by immobilizing the animal and geometric-distortion artifacts are reduced by accurately positioning the animal to improve static-field shimming. The RF coil, in turn, must provide high sensitivity over the whole brain and not physically interfere with the animal holder. To accomplish these tasks, the animal holder and RF coil should be designed in tandem. In this manuscript, animal holders and RF coils for mice, rats, and marmoset monkeys are described. Each animal holder includes components for anesthesia delivery and animal immobilization, as well as a compatible receive coil. RESULTS/COMPARISON WITH EXISTING METHOD(S): Animal holders were capable of accurate and reproducible positioning (for the marmoset, this was in the stereotactic plane), consequently reducing geometric distortion in echo-planar images. Ear bars were designed in conjunction with receive-coil formers, thereby maximizing the sensitive region of coils, while concurrently reducing motion to less than a pixel over EPI time series. Motion and SNR were quantified to facilitate direct comparison to existing animal holders and RF coils. All computer-aided-design (CAD) files of animal holders and RF coils are provided to promote dissemination. CONCLUSIONS: The confluence of design between the animal holder and RF coil provides a pragmatic solution for routine imaging of small animals.


Subject(s)
Brain/diagnostic imaging , Magnetic Resonance Imaging/instrumentation , Magnetic Resonance Imaging/methods , Stereotaxic Techniques/instrumentation , Animals , Artifacts , Brain/anatomy & histology , Brain/physiology , Callithrix , Equipment Design , Mice , Radio Waves , Rats , Reproducibility of Results , Signal-To-Noise Ratio
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