BACKGROUND At least 60% of those treated for an alcohol use disorder will relapse. Empirical study of the integrity of the brain reward system (BRS) is critical to understanding the mechanisms of relapse as this collection of circuits is implicated in the development and maintenance of all forms of addictive disorders. This study compared thickness, surface area and volume in neocortical components of the BRS among non-smoking light drinking controls (Controls), individuals who remained abstinent and those who relapsed after treatment. METHODS Seventy-five treatment-seeking alcohol dependent individuals (abstinent for 7 ± 3 days) and 43 Controls completed 1.5T proton magnetic resonance imaging studies. Parcellated morphological data was obtained for following bilateral components of the BRS: rostral and caudal anterior cingulate cortex, insula, medial and lateral orbitofrontal cortex, rostral and caudal middle and superior frontal gyri, amygdala and hippocampus as well as for 26 other bilateral neocortical regions. Alcohol dependent participants were followed over 12-months after baseline study and were classified as Abstainers (no alcohol consumption; n=24) and Relapsers (any alcohol consumption; n=51) at follow-up. RESULTS Relapsers and Abstainers demonstrated lower cortical thickness in the vast majority of BRS regions as well as lower global thickness compared to Controls. Relapsers had lower total BRS surface area than both Controls and Abstainers, but Abstainers were not significantly different from Controls on any surface area measure. Relapsers demonstrated lower volumes than Controls in the majority of regions, while Abstainers showed lower volumes than Controls in the superior frontal gyrus, insula, amygdala and hippocampus, bilaterally. Relapsers exhibited smaller volumes than Abstainers in the right rostral middle and caudal middle frontal gyri and the lateral orbitofrontal cortex, bilaterally. In Relapsers, lower baseline volumes and surface areas in multiple regions were associated with a greater magnitude of post-treatment alcohol consumption. CONCLUSIONS Results suggest Relapsers demonstrated morphological abnormalities in regions involved in the “top down” regulation/modulation of internal drive states, emotions, reward processing and behavior, which may impart increased risk for the relapse/remit cycle that afflicts many with an AUD. Results also highlight the importance of examining both cortical thickness and surface area to better understand the nature of regional volume loss frequently observed in AUD. Results from this report are consistent with previous research implicating plastic neurobiological changes the brain reward system in the maintenance of addictive disorders.

We compared the predictive value of cerebral perfusion as measured by arterial-spin labeling magnetic resonance imaging (ASL-MRI) with MRI-derived hippocampal volume for determining future cognitive and functional decline and subsequent conversion from mild cognitive impairment to dementia. Forty-eight mild cognitive impairment subjects received structural and ASL-MRI scans at baseline and clinical and neuropsychologic assessments annually. Thirteen subjects became demented during the period of longitudinal observation (2.7 ± 1.0 y). Cox regression analyses suggest that baseline hippocampal volume [relative risk (RR) = 0.99, P = 0.004], baseline right inferior parietal (RR = 0.64, P = 0.01) and right middle frontal (RR = 0.73, P = 0.01) perfusion were associated with conversion to dementia. Results from linear mixed effects modeling suggest that baseline perfusion from the right precuneus predicted subsequent declines in Clinical Dementia Rating Sum of Boxes (P = 0.002), Functional Activates Questionnaire (P = 0.01), and selective attention (ie, Stroop switching, P = 0.009) whereas baseline perfusion from the right middle frontal cortex predicted subsequent episodic memory decline (ie, total recognition discriminability score from the California Verbal Learning Test, P = 0.03). These results suggest that hypoperfusion as detected by ASL-MRI can predict subsequent clinical, functional, and cognitive decline and may be useful for identifying candidates for future Alzheimer disease treatment trials. Keywordsmild cognitive impairment; dementia; cognitive and functional decline; ASL perfusion MRI; hippocampal volume Mild cognitive impairment (MCI) is considered to be the transition between normal aging and Alzheimer disease (AD), the most prevalent dementing disorder in older adults. Studies with fluorodeoxyglucose (FDG) positron emission tomography (PET), which measures glucose metabolism, and technetium-99m hexamethylpropyleneamineoxime single photon emission NIH Public Access Author ManuscriptAlzheimer Dis Assoc Disord. Author manuscript; available in PMC 2010 May 6. Published in final edited form as:Alzheimer 7 ,8 and hippocampus, 6,9-11 are sensitive early markers of progression to AD. Using principal component analysis, Borroni et al 12 described a specific pattern of hypoperfusion in converters that involved the parietal and temporal lobes, precuneus and posterior cingulate cortex. Caroli et al 13 recently reported that compared with control subjects, amnestic MCI who converted to AD had hypoperfusion in the parahippocampal and inferior temporal cortices whereas amnestic MCI patients who did not convert to dementia had hypoperfusion in the retrosplenial cortex.To the extent that regional metabolism and perfusion are coupled, arterial spin-labeling magnetic resonance imaging (ASL-MRI), which labels arterial blood water as an endogenous diffusible tracer for perfusion, may be able to detect functional deficiencies in a way similar to FDG PET and SPECT. 14 In support of this, ASL-MRI studies of AD and...

Summary:Purpose: In temporal lobe epilepsy (TLE) with evidence of hippocampal sclerosis (TLE-MTS) volumetric gray (GM) and white (WM) matter abnormalities are not restricted to the hippocampus but also are found in extrahippocampal structures. Less is known about extrahippocampal volumetric abnormalities in TLE without hippocampal sclerosis (TLE-no). In this study, we used optimized voxel-based morphometry (VBM) with and without modulation with the following aims: (a) to identify WM and GM abnormalities beyond the hippocampus in TLE-MTS and TLE-no; and (b) to determine whether extratemporal WM and GM abnormalities differ between TLE-MTS and TLEno.Methods: Optimized VBM of GM and WM with and without modulation was performed in 26 TLE-MTS (mean age, 35.6 ± 9.7 years), 17 TLE-no (mean age, 35.6 ± 11.1 years), and 30 healthy controls (mean age, 30.3 ± 11.1 years).Results: In TLE-MTS, GM/WM volume and concentration reductions were found in the ipsilateral limbic system, ipsi-and contralateral neocortical regions, thalamus, cerebellum, internal capsule, and brainstem when compared with controls. In contrast, no differences of GM/WM volumes/concentrations were found between TLE-no and controls or between TLE-no and TLE-MTS.Conclusions: In TLE-MTS, optimized VBM showed extensive GM and WM volume reductions in the ipsilateral hippocampus and in ipsi-and contralateral extrahippocampal regions. In contrast, no GM/WM volume or concentration reductions were found in TLE-no. This further supports the hypothesis that TLE-no is a distinct clinicopathologic entity from TLE-MTS and probably heterogeneous in itself. Key Words: TLE-Extratemporal-Voxel-based morphometryMesiotemporal sclerosis-Normal MRI.Mesial temporal lobe epilepsy (mTLE) is one of most frequent forms of partial epilepsy in adults. Based on neuroimaging and histologic characteristics, two main subtypes of mTLE can be distinguished: (a) TLE with hippocampal sclerosis (TLE-MTS), found in ∼60-70% of mTLE patients, which is characterized by an increased hippocampal T 2 signal and/or atrophied hippocampal formation on the MRI and significant neuronal loss in one or more hippocampal subfields in the histologic examination (1); and (b) MTLE without structural abnormalities on MRI (TLE-no) and only very mild or no neuronal loss in the hippocampus, which is found in ∼20-30% of mTLE patients. In both types of mTLE, seizures are not restricted to the medial temporal lobe but involve

Background Parkinson’s disease (PD) is histopathologically characterized by the loss of dopamine neurons in the substantia nigra pars compacta. The depletion of these neurons is thought to reduce the dopaminergic function of the nigrostriatal pathway, as well as the neural fibers that link the substantia nigra to the striatum (putamen and caudate), causing a dysregulation in striatal activity that ultimately leads to lack of movement control. Based on diffusion tensor imaging, visualizing this pathway and measuring alterations of the fiber integrity remain challenging. The objectives were to: 1) develop a diffusion tensor tractography protocol for reliably tracking the nigrostriatal fibers on multicenter data; 2) test whether the integrities measured by diffusion tensor imaging of the nigrostriatal fibers are abnormal in PD; 3) test if abnormal integrities of the nigrostriatal fibers in PD patients are associated with the severity of motor disability and putaminal dopamine binding ratios. Methods Diffusion tensor tractography was performed on 50 drug naïve PD patients and 27 healthy control subjects from the international multicenter Parkinson’s Progression Marker Initiative. Results Tractography consistently detected the nigrostriatal fibers, yielding reliable diffusion measures. Fractional anisotropy, along with radial and axial diffusivity of the nigrostriatal tract, showed systematic abnormalities in patients. In addition, variations in fractional anisotropy and radial diffusivity of the nigrostriatal tract were associated with the degree of motor deficits in PD patients. Conclusion Taken together, the findings imply that the diffusion tensor imaging characteristic of the nigrostriatal tract is potentially an index for detecting and staging of early PD.

To characterize and compare measurements of the posterior cingulate glucose metabolism, the hippocampal glucose metabolism, and hippocampal volume so as to distinguish cognitively normal, late-middleaged persons with 2, 1, or 0 copies of the apolipoprotein E (APOE) ε4 allele, reflecting 3 levels of risk for lateonset Alzheimer disease.Design: Cross-sectional comparison of measurements of cerebral glucose metabolism using 18 F-fluorodeoxyglucose positron emission tomography and measurements of brain volume using magnetic resonance imaging in cognitively normal ε4 homozygotes, ε4 heterozygotes, and noncarriers.Setting: Academic medical center.Participants: A total of 31 ε4 homozygotes, 42 ε4 heterozygotes, and 76 noncarriers, 49 to 67 years old, matched for sex, age, and educational level. Main Outcome Measures:The measurements of posterior cingulate and hippocampal glucose metabolism were characterized using automated region-of-interest algorithms and normalized for whole-brain measurements. The hippocampal volume measurements were charac-terized using a semiautomated algorithm and normalized for total intracranial volume.Results: Although there were no significant differences among the 3 groups of participants in their clinical ratings, neuropsychological test scores, hippocampal volumes (P=.60), or hippocampal glucose metabolism measurements (P = .12), there were significant group differences in their posterior cingulate glucose metabolism measurements (P =.001). The APOE ε4 gene dose was significantly associated with posterior cingulate glucose metabolism (r = 0.29, P = .0003), and this association was significantly greater than those with hippocampal volume or hippocampal glucose metabolism (PϽ.05, determined by use of pairwise Fisher z tests).Conclusions: Although our findings may depend in part on the analysis algorithms used, they suggest that a reduction in posterior cingulate glucose metabolism precedes a reduction in hippocampal volume or metabolism in cognitively normal persons at increased genetic risk for Alzheimer disease.

The overall goal was to identify patterns of brain atrophy associated with cognitive impairment and future cognitive decline in non-demented elders. Seventy-one participants were studied with structural MRI and neuropsychological testing at baseline and 1 year follow-up. Deformationbased morphometry was used to examine the relationship between regional baseline brain tissue volume with baseline and longitudinal measures of delayed verbal memory, semantic memory, and executive function. Smaller right hippocampal and entorhinal cortex (ERC) volumes at baseline were associated with worse delayed verbal memory performance at baseline while smaller left ERC volume was associated with greater longitudinal decline. Smaller left superior temporal cortex at baseline was associated with worse semantic memory at baseline, while smaller left temporal white and gray matter volumes were associated with greater semantic memory decline. Increased CSF and smaller frontal lobe volumes were associated with impaired executive function at baseline and greater longitudinal executive decline. These findings suggest that baseline volumes of prefrontal and temporal regions may underlie continuing cognitive decline due to aging, pathology, or both in non-demented elderly individuals.

Although routine nigral measurements of fractional anisotropy are clinically not helpful, the findings in this study suggest that more-sophisticated diffusion imaging protocols should be used when exploring the clinical utility of this imaging modality.

We sought to determine whether there are structural and metabolic changes in the brains of older adults with cognitive complaints yet who do not meet MCI criteria (i.e., preMCI). We compared the volumes of regional lobar gray matter (GM) and medial temporal lobe structures, including the hippocampus, entorhinal cortex (ERC), fusiform and parahippocampal gyri, and metabolite ratios from the posterior cingulate in individuals who had a Clinical Demetia Rating (CDR) of 0.5, but who did not meet MCI criteria (preMCI, N = 17), patients with mild cognitive impairment (MCI, N = 13), and cognitively normal controls (N = 18). Controls had more ERC, fusiform, and frontal gray matter volume than preMCI and MCI subjects and greater parahippocampal volume and more posterior cingulate N-acetylaspartate (NAA)/myoinosotil (mI) than MCI. There were no significant differences between MCI and preMCI subjects on any of these measures. These findings suggest there are neurodegenerative changes in the brains of older adults who have cognitive complaints severe enough to qualify for CDR = 0.5 yet show no deficits on formal neuropsychological testing. The results further support the hypothesis that detection of individuals with very mild forms of Alzheimer's disease (AD) may be facilitated by use of the CDR, which emphasizes changes in cognition over time within individuals rather than comparison with group norms.