The ability to stand quietly is disturbed by degradation of cerebellar systems. Given the complexity of sensorimotor integration invoked to maintain upright posture, the integrity of supratentorial brain structures may also contribute to quiet standing and consequently be vulnerable to interference from cognitive challenges. As cerebellar system disruption is a common concomitant of alcoholism, we examined 46 alcoholics and 43 controls with a force platform to derive physiological indices of quiet standing during cognitive (solving simple, mental arithmetic problems) and visual (eyes closed) challenges. Also tested were relations between tremor velocity and regional gray matter and white matter tissue quality measured with the diffusion tensor imaging (DTI) metric of mean diffusivity (MD), indexing disorganized microstructure. Spectral analysis of sway revealed greater tremor in alcoholic men than alcoholic women or controls. Cognitive dual-tasking elicited excessive tremor in two frequency bands, each related to DTI signs of degradation in separate brain systems: tremor velocity at a low frequency (2-5 Hz/0-2 Hz) correlated with higher MD in the cerebellar hemispheres and superior cingulate bundles, whereas tremor velocity at a higher frequency (5-7 Hz) correlated with higher MD in the motor cortex and internal capsule. These brain sites may represent “tremorgenic networks” that, when disturbed by disease and exacerbated by cognitive dual-tasking, contribute to postural instability, putting affected individuals at heightened risk for falling.
Dynamic Responses of Selective Brain White Matter Fiber Tracts to Binge Alcohol and Recovery in the Rat
To determine the dynamics of white matter vulnerability to excessive alcohol consumption, diffusion tensor imaging (DTI) was used in an animal model of alcohol exposure.
Quantitative Susceptibility Mapping by Inversion of a Perturbation Field Model: Correlation with Brain Iron in Normal Aging
There is increasing evidence that iron deposition occurs in specific regions of the brain in normal aging and neurodegenerative disorders such as Parkinson’s, Huntington’s, and Alzheimer’s disease. Iron deposition changes the magnetic susceptibility of tissue, which alters the MR signal phase, and allows estimation of susceptibility differences using quantitative susceptibility mapping (QSM). We present a method for quantifying susceptibility by inversion of a perturbation model, or “QSIP.” The perturbation model relates phase to susceptibility using a kernel calculated in the spatial domain, in contrast to previous Fourier-based techniques. A tissue/air susceptibility atlas is used to estimate B0 inhomogeneity. QSIP estimates in young and elderly subjects are compared to postmortem iron estimates, maps of the Field-Dependent Relaxation Rate Increase, and the L1-QSM method. Results for both groups showed excellent agreement with published postmortem data and in vivo FDRI: statistically significant Spearman correlations ranging from Rho=0.905 to Rho=1.00 were obtained. QSIP also showed improvement over FDRI and L1-QSM: reduced variance in susceptibility estimates and statistically significant group differences were detected in striatal and brainstem nuclei, consistent with age-dependent iron accumulation in these regions.
Compromised Frontocerebellar Circuitry Contributes to Nonplanning Impulsivity in Recovering Alcoholics
Degradation of frontocerebellar circuitry is a principal neural mechanism of alcoholism-related executive dysfunctions affecting impulse control and cognitive planning.
We tested the hypothesis that alcoholic patients would demonstrate compromised dorsal anterior cingulate cortex (dACC) -cerebellar functional connectivity when adjusting their strategies to accommodate uncertain conditions and would recruit compensatory brain regions to overcome ineffective response patterns.
Twenty-six alcoholics and 26 healthy participants underwent functional MRI in two sequential runs while performing a decision-making task. The first run required a response regardless of level of ambiguity of the stimuli; the second run allowed a PASS option (i.e., no response choice), which was useful on ambiguous trials.
Healthy controls demonstrated strong synchronous activity between the dACC and cerebellum while planning and executing a behavioral strategy. By contrast, alcoholics showed synchronous activity between the dACC and the premotor cortex, perhaps enabling successful compensation for accuracy and reaction time in certain conditions; however, a negative outcome of this strategy was rigidity in modifying response strategy to accommodate uncertain conditions. Compared with the alcoholic group, the control group had lower nonplanning impulsiveness, which correlated with using the option PASS to respond in uncertain conditions.
These findings suggest that compromised dACC-cerebellar functional circuitry contributes to recruitment of an alternative network-dACC-premotor cortex- to perform well under low-risk, unambiguous conditions. This compensatory network, however, was inadequate to enable the alcoholics to avert making poor choices in planning and executing an effective behavioral strategy in high-risk, uncertain conditions.
Neuroinflammatory mechanisms contribute to the brain pathology resulting from human immunodeficiency virus (HIV) infection. Magnetic resonance spectroscopy (MRS) has been touted as a suitable method for discriminating in vivo markers of neuroinflammation. The present MRS study was conducted in four groups: alcohol dependent (A, n = 37), HIV-infected (H, n = 33), alcohol dependent + HIV infected (HA, n = 38) and healthy control (C, n = 62) individuals to determine whether metabolites would change in a pattern reflecting neuroinflammation. Significant four-group comparisons were evident only for striatal choline-containing compounds (Cho) and myo-inositol (mI), which follow-up analysis demonstrated were due to higher levels in HA compared with C individuals. To explore the potential relevance of elevated Cho and mI, correlations between blood markers, medication status and alcohol consumption were evaluated in H + HA subjects. Having an acquired immune deficiency syndrome (AIDS)-defining event or hepatitis C was associated with higher Cho; lower Cho levels, however, were associated with low thiamine levels and with highly active antiretroviral HIV treatment (HAART). Higher levels of mI were related to greater lifetime alcohol consumed, whereas HAART was associated with lower mI levels. The current results suggest that competing mechanisms can influence in vivo Cho and mI levels, and that elevations in these metabolites cannot necessarily be interpreted as reflecting a single underlying mechanism, including neuroinflammation.
Interhemispheric Functional Connectivity Change Is Linked to Callosal Fiber Integrity Change over a 1-Year Follow-up in Chronic Alcoholics
Chronic alcoholism has deleterious long-term effects on the integrity of callosal white matter fibers connecting the two cerebral hemispheres. We tested whether microstructural fiber changes relate to resting-state functional connectivity changes in alcoholics who have maintained sobriety during a one-year interval, and whether these changes are beyond those potentially exhibited by controls. 12 (7w, 5m) alcoholics (ALC) and 13 (7w, 6m) age-matched controls (CTL) underwent MR diffusion tensor imaging and functional MR imaging at baseline and 1-year follow-up. In ALC, age at alcoholism onset was on average 37 years (range 15-56 years); the average time since last drink before study entry was 3½ months for ALC. Within the 1-year follow-up period, 6 ALC remained sober and 6 resumed drinking at social levels. We examined effects of group (CTL, ALC) and time (baseline, 1 year) on fractional anisotropy (FA) and mean diffusivity (MD) of fiber tufts of the whole corpus callosum and of 7 callosal sectors quantified with fiber tracking. Functional connectivity between the left and right hemisphere was tested for group and time, for 8 bilaterally homologous cortical areas: anterior, dorsolateral, and medial prefrontal, motor, parietal, occipital, medial and lateral temporal. Alcoholics showed poorer callosal fiber integrity (lower FA, higher MD) than CTL, with 3-way interactions for FA and MD indicating continued microstructural decline over the year in ALC relative to CTL that was more pronounced in anterior than posterior callosal sectors. Overall, groups did not differ in interhemispheric functional connectivity strength; a group-by-time interaction indexed a connectivity decline over the year between lateral temporal cortices in ALC relative to CTL. Higher amounts of lifetime alcohol consumption correlated with continued decline in callosal FA and with change to weaker interhemispheric connectivity between motor regions in ALC and between temporal regions over both groups. Within alcoholics, 1-year change to weaker functional connectivity between left and right medial frontal, motor, medial temporal and occipital regions was associated with continued decline in callosal white matter (FA, MD). To the extent that callosal fibers support interhemispheric cortico-cortical functional connectivity, these data suggest that continued fiber degradation is accompanied by decline in interhemispheric functional connectivity strength. Thus, continued decline in callosal fiber integrity occurs in alcoholism despite sobriety and relates to weaker interhemispheric functional connections in ALC, specifically in those with heavier past lifetime drinking.
In Vivo Diffusion Tensor Imaging Evidence for Reversible White Matter Microstructural Integrity Disruption: Effects of Abstinence in Rat and Man
SRI Authors: Natalie Zahr, Adolf Pfefferbaum
SRI Authors: Adolf Pfefferbaum, Tilman Schulte
Substantial brain development occurs during adolescence providing the foundation for functional advancement from stimulus-bound “bottom-up” to more mature executive-driven “top-down” processing strategies. The objective was to assess development of EEG markers of these strategies and their role in both preparatory attention (contingent negative variation, CNV) and response monitoring (Error Related Negativity, ERN, and Correct Related Negativity, CRN).
CNV, ERN and CRN were assessed in 38 adolescents (18 girls), age 11–18 years, using a variation of a letter discrimination task.
Accuracy increased with age and developmental stage. Younger adolescents used a posterior attention network involved in inhibiting irrelevant information. Activity in this juvenile network, as indexed by a posteriorly-biased CNV and CRN decreased with age and advancing pubertal development. Although enhanced frontal CNV, known to be predictive of accuracy in adults, was not detected even in the older adolescents, top-down medial frontal response monitoring processes (ERN) showed evidence of development within the age-range studied.
The data revealed a dissociation of developmental progress, marked by relatively delayed onset of frontal preparatory attention relative to error monitoring.
This dissociation may render adolescents vulnerable to excessive risk-taking and disinhibited behavior imposed by asynchronous development of component cognitive control processes.