Search

The cerebellum recognizes sequences from prior experiences and uses this information to generate internal models that predict future outcomes in a feedforward manner [Front Hum Neurosci 8: 475, 2014; Cortex 47: 137-44, 2011; Cerebellum 7: 611-5, 2008; J Neurosci 26: 9107-16, 2006]. This process has been well documented in the motor domain, but the cerebellum's role in cognitive sequencing, within the context of implicit versus explicit processes, is not well characterized. In this study, we tested individuals with cerebellar ataxia and healthy controls to clarify the role of the cerebellum sequencing using variations on implicit versus explicit and motor versus cognitive demands across five experiments. Converging results across these studies suggest that cerebellar feedforward mechanisms may be necessary for sequencing in the implicit domain only. In the ataxia group, rhythmic tapping, rate of motor learning, and implicit sequence learning were impaired. However, for cognitive sequencing that could be accomplished using explicit strategies, the cerebellar group performed normally, as though they shifted to extra-cerebellar mechanisms to compensate. For example, when cognitive and motor functions relied on cerebellar function simultaneously, the ataxia group's motor function was unaffected, in contrast to that of controls whose motor performance declined as a function of cognitive load. These findings indicated that the cerebellum is not critical for all forms of sequencing per se. Instead, it plays a fundamental role for sequencing within the implicit domain, whether functions are motor or cognitive. Moreover, individuals with cerebellar ataxia are generally able to compensate for cognitive sequencing when explicit strategies are available in order to preserve resources for motor function.

In the original article, the legend within Fig. 3 incorrectly read as ‘*p 0.01’. This has now been changed to ‘*p

Isolated cleft lip and/or palate (ICLP) is one of the most common congenital birth defects in the USA, affecting roughly 1 in 600 births annually. Along with the facial deformity, this population has been found to have abnormal neurodevelopment and gross structural abnormalities in the brain, particularly within the cerebellum. The current study examined cerebellar structure within the two primary subtypes of ICLP: cleft lip with/without cleft palate (CL/P) and cleft palate alone (CPO). A large sample of 107 subjects aged 7 to 27 years with ICLP was compared to 127 healthy controls. Samples were separated by sex. Brain structure was obtained via magnetic resonance imaging. For males, after controlling for intracranial volume, cerebellum volume was significantly lower in the ICLP group (F = 12.351, p = 0.001). Regionally in the cerebellum, males with ICLP had proportionally larger anterior lobes (F = 4.022, p = 0.047) and smaller superior posterior lobes (F = 5.686, p = 0.019). CL/P males showed only a reduction in overall cerebellum volume, with no regional changes. CPO males showed only regional changes, with no reduction in overall volume. Females with ICLP showed no overall or regional cerebellar abnormalities. However, females with CPO did have significantly lower cerebellum volumes than controls. The results reveal both global and regional cerebellar abnormalities within subjects with ICLP. They also establish the existence of abnormal cerebellar morphologies that are dependent on cleft subtype as well as sex. This lends further support to the claim that CL/P and CPO are distinct conditions.

Environmental factors may contribute as much as one-third of the variance in Huntington disease (HD) age of onset. Substance abuse is a risk factor for other neurodegenerative disorders; however, whether substance abuse influences HD age of onset is not well established. This study investigated the relationships between alcohol, drug, and tobacco abuse and HD age of onset in 136 participants with symptomatic HD. CAG repeat length was used as a covariate in all analyses, as it represents the most significant determinant of HD age of onset. The relationship between substance abuse, HD age of onset, and sex was also examined, as women may experience greater medical harm from substance abuse. Lifetime alcohol abuse and lifetime drug abuse were associated with earlier age of HD onset; a similar trend was seen for current tobacco abuse. For women, lifetime alcohol abuse was associated with earlier onset of HD, with a similar trend for lifetime drug abuse. However, alcohol, drug, and tobacco abuse were not significantly associated with age of onset in men. Further work is needed to determine whether substance abuse is a causative risk factor for earlier onset of HD, and why the environmental factors associated with age of onset vary by sex.

Diffusion tensor imaging was used to study brain related changes in white matter that may be associated with Huntington’s Disease progression. Thirty-one preclinical gene-mutation carriers were imaged cross-sectionally using diffusion tensor and anatomical brain imaging. Subjects were individuals who had a known gene mutation for HD but did not manifest motor diagnostic criteria for HD. Fractional anisotropy scalar maps showed a positive correlation with five year probability of diagnosis (based upon gene repeat length and current age) in the putamen and a negative correlation in the external capsule. This study shows that scalar maps generated from diffusion tensor imaging may be directly related to the earliest stages of disease progression within HD, even before a diagnosis is given. Findings suggest that DTI measures, therefore, may have the ability to act as a biomarker for disease progression in clinical trials of pre-manifest subjects.

Background: Early stages of chronic obstructive pulmonary disease (COPD) are characterized by loss of the terminal bronchioles and ‘air trapping’ often before overt emphysema manifests (1). COPD patients are also at risk for cardiovascular disease (CVD), therefore, we hypothesized that the degree of air trapping on computed tomography (CT) (2) would be associated with higher aortic (carotid femoral pulse wave velocity, CFPWV) and carotid artery stiffness (β-stiffness), biomarkers of CVD risk. Methods: Ten adults with COPD but little emphysema (age 66±8 yrs, 5F/5M, GOLD stage 1–3) and 9 adults without COPD (age 59±13 yrs, 5F/4M) that had a research chest CT were recruited. Results: COPD patients had greater smoking history (45.9 ± 21 vs. 6.4 ± 12.9 pack-years, P0.05). COPD patients had significantly higher CFPWV (999± 293 vs. 760 ±147 cm/sec, p

Background PREDICT-HD is a large multi-site study of individuals with the HD gene expansion who have not yet been diagnosed with the disorder (pre-HD), as well as a smaller group of gene-negative control subjects. Subjects have been followed-up yearly with extensive neuropsychological testing, clinical evaluation, and psychiatric assessment, and every two years with MRI. Methods The sample used for the current analysis included 215 pre-HD participants, 35 individuals newly diagnosed with HD, and 47 age- and sex-matched control subjects. At least two scans, obtained with an interscan interval of 2 years, were analyzed for each subject. Measurements included volumes of caudate, putamen, thalamus, gray, and white matter. Pre-HD subjects were divided into groups based on their estimated proximity to onset (Far, >15 years; Mid, 9-15 years; and Near, Results Longitudinal change in striatal volume was greater for the Mid, Near, and Diagnosed subjects than for the Control or Far subjects. There was no significant difference between the Far and Control subjects for amount of longitudinal change, and no significant differences among the Mid, Near, and Diagnosed groups. Results for caudate and putamen were the same as those for total striatal volume change. For thalamus, Near and Diagnosed subjects had greater longitudinal change than the other three groups. Effect sizes were calculated, as well as power analyses to demonstrate the number of subjects per treatment group that would be necessary for trials conducted at each preclinical stage. Data for total gray and white volume will also be presented. Conclusions Disease-related longitudinal change in striatal volume is observable over a two-year period in individuals who are within 15 years of estimated disease onset, and rate of change is fairly consistent over time once it begins. Observable longitudinal change for the thalamus begins later in the disease process.

Objective To present data from 32 converter participants and 80 matched non-converter participants from the PREDICT-HD study. Methods All participants were prodromal when they enrolled in the study and all were examined yearly for at least one visit following enrollment. Converters were defined as those individuals who, on at least two consecutive visits, received a score of 4 on the HD Diagnostic Confidence Scale of the UHDRS. Non-converters were individuals who had at least two visits and never received a score of 4. Converters and non-converters were group-matched on age, gender, and CAG repeat length. MRI measurements were obtained for 4 converters 2 years before diagnosis, for 11 converters 1 year before diagnosis, and for 17 converters at the same visit that the diagnosis was made. Results and Discussion After correcting for intracranial volume (ICV), converters had significantly smaller total brain volume (p = 0.001), total white matter volume (p = 0.004), and total striatum volume (p