Are different languages anatomically segregated in the brains of some proficient bilinguals? Behavioral and neuropsychological studies of this question have produced conflicting results. One early functional magnetic resonance imaging (fMRI) study [Kim et al., 1997, Nature 388:171] reported significant segregation between languages in Broca's area when late bilinguals performed an open-ended language production task. Subsequent fMRI studies, utilizing more state-of-the-art methods, have failed to find evidence of such segregation, but these studies also used more constrained linguistic tasks (typically comprehension tasks). We report the results of an fMRI experiment utilizing Kim et al.'s (1997) silent production task, but using state-of-the-art methods. Eight right-handed, proficient, late bilinguals participated in three conditions during a blocked, fMRI experiment: (1) silent, open-ended production in their first language (L1), (2) silent, open-ended production in their second language (L2), and (3) fi...

The definitive diagnosis of Alzheimer's disease (AD) currently requires post-mortem examination. We present a novel method for the detection of amyloid β (Aβ) plaques by magnetic resonance micro-imaging (μMRI) using transgenic mouse models of AD. This method utilizes Aβ1-40 peptides, which are labeled with either gadolinium (Gd) or monocrystalline iron oxide nanoparticles (MION). When either of these ligands is injected in vivo systemically with mannitol to transiently open the blood-brain-barrier, we are able to image both ex vivo and in vivo the majority of Aβ plaques. No lesions are detected in the non-Tg mice injected with these ligands. Tg mice injected with Aβ not coupled to Gd or MION also showed no lesions. This μMRI approach can be used to monitor potential therapeutic amyloid clearance in AD model mice in vivo and with further development could be the basis for plaque detection in AD patients.

Parkinson’s disease (PD) is a progressive neurodegenerative disease that is typically diagnosed late in its progression. There is a need for biomarkers suitable for monitoring the disease progression at earlier stages to guide the development of novel neuroprotective therapies. One potential biomarker, α-synuclein, has been found in both the familial cases of PD, as well as the sporadic cases and is considered a key feature of PD. α-synuclein is naturally present in the retina, and it has been suggested that early symptoms of the visual system may be used as a biomarker for PD. Here, we use a viral vector to induce a unilateral expression of human wildtype α-synuclein in rats as a mechanistic model of protein aggregation in PD. We employed functional magnetic resonance imaging (fMRI) to investigate whether adeno-associated virus (AAV) mediated expression of human wildtype α-synuclein alter functional activity in the visual system. 16 rats were injected with either AAV-α-synuclein (n=7) or AAV-null (n=9) i...

The linear transform model of functional magnetic resonance imaging (fMRI) hypothesizes that fMRI responses are proportional to local average neural activity averaged over a period of time. This work reports results from three empirical tests that support this hypothesis. First, fMRI responses in human primary visual cortex (V1) depend separably on stimulus timing and stimulus contrast. Second, responses to long-duration stimuli can be predicted from responses to shorter duration stimuli. Third, the noise in the fMRI data is independent of stimulus contrast and temporal period. Although these tests can not prove the correctness of the linear transform model, they might have been used to reject the model. Because the linear transform model is consistent with our data, we proceeded to estimate the temporal fMRI impulse–response function and the underlying (presumably neural) contrast–response function of human V1.

Parkinson’s disease (PD) is a progressive neurodegenerative disease that is typically diagnosed late in its progression. There is a need for biomarkers suitable for monitoring the disease progression at earlier stages to guide the development of novel neuroprotective therapies. One potential biomarker, α-synuclein, has been found in both the familial cases of PD, as well as the sporadic cases and is considered a key feature of PD. α-synuclein is naturally present in the retina, and it has been suggested that early symptoms of the visual system may be used as a biomarker for PD. Here, we use a viral vector to induce a unilateral expression of human wild-type α-synuclein in rats as a mechanistic model of protein aggregation in PD. We employed functional magnetic resonance imaging (fMRI) to investigate whether adeno-associated virus (AAV) mediated expression of human wild-type α-synuclein alter functional activity in the visual system. A total of 16 rats were injected with either AAV-α-synuclein ( n  = 7) or ...

Background and Purpose: Severe perinatal aphyxia is an important cause of brain injury in the newborn infant. We examined if the early events after hypoxic ischemia (HI) in the 7-day-old mouse brain detected by magnetic resonance imaging (MRI) were related to and the long-term functional effects assessed in the same animals at 4 weeks of age. Methods: Hypoxic ischemia was induced in 7-day-old CD1 mice by exposure to 8% oxygen for 30 minutes after occlusion of the left common carotid artery. The resulting unilateral focal lesion was evaluated in vivo by MRI (T2 maps, ADC maps) at 3, 6, 24 hours and 5 days after hypoxia. Locomotion and sensorimotor function were analysed after 3 weeks. After 4 weeks morphological evaluation was performed on cresyl violet stained brain slices. Results: A decrease in ADC-values in cortex on the affected side was found at 3 hours after reperfusion. A significant increase in T2-values was seen after 6h to 5 days. Maximal size of the lesion was attained at 3-6 hours after reperfu...

Introduction In this work we investigate how the hemodynamic changes evoked by D-amphetamine in normal and MPTP treated monkeys can be mapped using pharmacologic MRI (phMRI) and PET to validate the degree of dopaminergic denervation after MPTP treatment. Methods Macaca Fascicularis: 6 normal control monkeys and 3 MPTP treated monkeys (2 with minor and 1 with severe PD symptoms). MRI phMRI images of cerebral blood volume changes were collected on a Siemen's 3T allegra system for 60-120 minutes (50sec/image set). 1.5-2.5mg/kg amphetamine was used to probe dopaminergic function. PET 11C-CFT was used to assess the binding potential of the dopamine transporter protein (DAT) in the striatum. Results Administration of amphetamine to control monkeys produced strong phMRI activation in caudate, putamen, accumbens, thalamus, and substantia nigra (increase in CBV between 10-35%). There was much less cortical activation compared to our prior rat phMRI studies. For the MPTP-treated monkeys with minor symptoms and moder...

Attention-Deficit Hyperactivity Disorder (ADHD) is the most common psychiatric disorder among school-aged children, occurring in about 5% of the population. Between 40-70% of these children also portray a persistent pattern of antisocial behavior, referred to as Conduct Disorder (CD). Researchers using MRI to study children with ADHD have consistently attributed core deficits of inattention and impulsivity to frontal-striatal-cerebellar abnormalities; however, no study has investigated the neuroanatomical characteristics of children diagnosed with ADHD co-morbid with CD. This study examined a community sample of 12 children with ADHD (aged 8-12, 7 with CD) and 24 healthy controls matched for age, sex, handedness, and SES. Volume measurements, including right-left asymmetries, were quantified from MRI of the total brain and cerebellar vermis. No significant differences in brain size or asymmetry were found between the groups. Measurements of the left and total posterior superior and inferior lobes of the ve...

A great deal is known about the response properties of single neurons processing sensory information. In contrast, less is understood about the collective characteristics of networks of neurons that may underlie sensory capacities of animals. We used functional magnetic resonance imaging to study the emergent properties of populations of neurons processing motion across different brain areas. Using a visual adaptation paradigm, we localized a distributed network of visual areas that process information about the direction of motion as expected from single-cell recording studies. However, we found an apparent discrepancy between the directional signals in certain visual areas as measured with blood oxygenation level-dependent imaging compared with an estimate based on the spiking of single neurons. We propose a hypothesis that may account for this difference based on the postulate that neuronal selectivity is a function of the state of adaptation. Consequently, neurons classically thought to lack informatio...

The relationship between limbic activity and emotional reactions to and enhanced memory for emotional material has been established for nonverbal stimuli. However, it is unknown whether this relationship holds for other stimuli such as words and whether it is modulated by individual differences in personality variables (e.g., Canli et al., 1999). We examined emotional memory and emotional reactions to verbal and nonverbal (photograph) stimuli using functional magnetic resonance imaging. The goals were to examine the neural correlates of emotional reactions to pleasant, unpleasant, and neutral verbal material, compare these correlates to the correlates of reactions to nonverbal material, and identify brain areas whose activity is correlated with memory for each type of emotional material. In addition, personality trait data were assessed to examine the possible modulatory role of personality characteristics. Functional imaging was conducted with a Philips 1.5 T ACS/NT scanner using gradient-recalled echo-pl...