The transition from adolescence to adulthood is associated with brain remodeling in the final stages of developmental growth. It is also a period when a large proportion of this age group engages in binge alcohol drinking (occasional consumption of four to five drinks leading to intoxication) and heavy alcohol drinking (binge drinking on ≥5 d in a month). Here we report on magnetic resonance imaging of developmental changes in the brain occurring during late adolescence and early adulthood (3.5–7.5 years of age) in a rhesus macaque model of alcohol self-administration. Monkeys were imaged prior to alcohol exposure, and following ∼6 and ∼12 months of daily (22 h/d) access to ethanol and water. The results revealed that the brain volume increases by 1 ml/1.87 years throughout the late adolescence and early adulthood in controls. Heavy alcohol drinking reduced the rate of brain growth by 0.25 ml/year per 1 g/kg daily ethanol. Cortical volume increased throughout this period with no significant effect of alcoh...

Amyloid deposition is present in 20–50% of nondemented older adults yet the functional consequences remain unclear. The current study found that amyloid accumulation is correlated with functional disruption of the default network as measured by intrinsic activity correlations. Clinically normal participants ( n = 38, aged 60–88 years) were characterized using 11C-labeled Pittsburgh Compound B positron emission tomography imaging to estimate fibrillar amyloid burden and, separately, underwent functional magnetic resonance imaging (fMRI). The integrity of the default network was estimated by correlating rest-state fMRI time courses extracted from a priori regions including the posterior cingulate, lateral parietal, and medial prefrontal cortices. Clinically normal participants with high amyloid burden displayed significantly reduced functional correlations within the default network relative to participants with low amyloid burden. These reductions were also observed when amyloid burden was treated as a cont...

Parkinson’s disease (PD) is characterized by the gradual degeneration of dopaminergic neurons in the substantia nigra, leading to striatal dopamine depletion. A partial unilateral striatal 6-hydroxydopamine (6-OHDA) lesion causes 40–60% dopamine depletion in the lesioned rat striatum, modeling the early stage of PD. In this study, we explored the connectivity between the brain regions in partially 6-OHDA lesioned male Wistar rats under urethane anesthesia using functional magnetic resonance imaging (fMRI) at 5 weeks after the 6-OHDA infusion. Under urethane anesthesia, the brain fluctuates between the two states, resembling rapid eye movement (REM) and non-REM sleep states. We observed clear urethane-induced sleep-like states in 8/19 lesioned animals and 8/18 control animals. 6-OHDA lesioned animals exhibited significantly lower functional connectivity between the brain regions. However, we observed these differences only during the REM-like sleep state, suggesting the involvement of the nigrostriatal dopa...

Laterality is a characteristic principle of the organization of the brain systems for language, and reduced hemispheric asymmetry has been considered a risk factor for schizophrenia. Here we sought support for the risk factor hypothesis by investigating whether reduced asymmetry of temporal lobe structure and function is also present in unaffected relatives. Sixteen schizophrenia patients, 16 age-matched first-degree relatives, and 15 healthy controls underwent high-resolution three-dimensional anatomical imaging and functional magnetic resonance imaging during auditory stimulation. Both the overall auditory cortex and planum temporale volumes and the lateralization to the left hemisphere were markedly reduced in patients. The decrease of lateralization correlated with increased severity of symptoms. In addition, both the overall functional activation in response to auditory stimulation and its asymmetry were reduced in the patients. Relatives had intermediate values between patients and controls on both s...

Previous imaging studies have reported differences in the neural networks supporting synchronized and syncopated sensorimotor coordination. Syncopation generates greater BOLD amplitude across a broad network that includes SMA, premotor cortex, cerebellum and basal ganglia. These regions are often ascribed roles in planning, preparation and timing leading to the hypothesis that while synchronization is carried out automatically, syncopation is planned on a movement by movement basis. This hypothesis suggests syncopated movements may be carried out in a discrete as opposed to rhythmic fashion. To investigate this at the neural level, we report here similarities and differences in the networks engaged for the performance of synchronized, syncopated and reactive movements. BOLD activity was measured while subjects (n=11) executed rhythmic or discrete sensorimotor coordination patterns. Subjects timed uni-manual finger opposition movements with respect to an auditory metronome delivered a constant rate (1.25 Hz...

Attending to a stimulus enhances the neuronal responses to it, while responses to nonattended stimuli are not enhanced and may even be suppressed. Although the neural mechanisms of response enhancement for attended stimuli have been intensely studied, the neural mechanisms underlying attentional suppression remain largely unknown. It is uncertain whether attention acts to suppress the processing in sensory cortical areas that would otherwise process the nonattended stimulus or the subcortical input to these cortical areas. Moreover, the neurochemical mechanisms inducing a reduction or suppression of neuronal responses to nonattended stimuli are as yet unknown. Here, we investigated how attention directed toward visual processing cross-modally acts to suppress vestibular responses in the human brain. By using functional magnetic resonance spectroscopy in a group of female and male subjects, we find that attention to visual motion downregulates in a load-dependent manner the concentration of excitatory neuro...

Genetic mutations in amyloid precursor protein (APP) and presenilin-1/2, each of which lead to an increase in toxic beta-amyloid, are linked to a high risk of Alzheimer’s disease (AD). However, the extent to which individual genetic variation affects ne...

Traumatic axonal injury (TAI) may contribute greatly to neurological impairments after traumatic brain injury, but it is difficult to assess with conventional imaging. We quantitatively compared diffusion tensor imaging (DTI) signal abnormalities with histological and electron microscopic characteristics of pericontusional TAI in a mouse model. Two DTI parameters, relative anisotropy and axial diffusivity, were significantly reduced 6 h to 4 d after trauma, corresponding to relatively isolated axonal injury. One to 4 weeks after trauma, relative anisotropy remained decreased, whereas axial diffusivity “pseudo-normalized” and radial diffusivity increased. These changes corresponded to demyelination, edema, and persistent axonal injury. At every time point, DTI was more sensitive to injury than conventional magnetic resonance imaging, and relative anisotropy distinguished injured from control mice with no overlap between groups. Remarkably, DTI changes strongly predicted the approximate time since trauma. Th...

Degeneration occurs differentially across cortical regions in amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS). Atrophy and cortical thinning is greatest in the precentral gyrus, but typically affects other cortical regions. Corre...

A hallmark feature of Huntington's disease pathology is the atrophy of brain regions including, but not limited to, the striatum. Though MRI studies have identified structural CNS changes in several Huntington's disease (HD) mouse models, the functional consequences of HD pathology during the progression of the disease have yet to be investigated using in vivo functional MRI (fMRI). To address this issue, we first established the structural and functional MRI phenotype of juvenile HD mouse model R6/2 at early and advanced stages of disease. Significantly higher fMRI signals [relative cerebral blood volumes (rCBVs)] and atrophy were observed in both age groups in specific brain regions. Next, fMRI results were correlated with electrophysiological analysis, which showed abnormal increases in neuronal activity in affected brain regions, thus identifying a mechanism accounting for the abnormal fMRI findings. [14C] 2-deoxyglucose maps to investigate patterns of glucose utilization were also generated. An intere...