Gray matter volume and pain tolerance in a general population: the Tromsø study.

ABSTRACT: As pain is processed by an extensive network of brain regions, the structural status of the brain may affect pain perception. We aimed to study the association between gray matter volume (GMV) and pain sensitivity in a general population. We used data from 1522 participants in the seventh wave of the Tromsø study, who had completed the cold pressor test (3°C, maximum time 120 seconds), undergone magnetic resonance imaging (MRI) of the brain, and had complete information on covariates. Cox proportional hazards regression models were fitted with time to hand withdrawal from cold exposure as outcome. Gray matter volume was the independent variable, and analyses were adjusted for intracranial volume, age, sex, education level, and cardiovascular risk factors. Additional adjustment was made for chronic pain and depression in subsamples with available information on the respective item. FreeSurfer was used to estimate vertexwise cortical and subcortical gray matter volumes from the T1-weighted MR image. Post hoc analyses were performed on cortical and subcortical volume estimates. Standardized total GMV was associated with risk of hand withdrawal (hazard ratio [HR] 0.81, 95% confidence interval [CI] 0.71-0.93). The effect remained significant after additional adjustment for chronic pain (HR 0.84, 95% CI 0.72-0.97) or depression (HR 0.82, 95% CI 0.71-0.94). In post hoc analyses, positive associations between standardized GMV and pain tolerance were seen in most brain regions, with larger effect sizes in regions previously shown to be associated with pain. In conclusion, our findings indicate that larger GMV is associated with longer pain tolerance in the general population.

High-Definition Transcranial Direct Current Stimulation Improves Delayed Memory in Alzheimer's Disease Patients: A Pilot Study Using Computational Modeling to Optimize Electrode Position.

BACKGROUND: The optimal stimulation parameters when using transcranial direct current stimulation (tDCS) to improve memory performance in patients with Alzheimer's disease (AD) are lacking. In healthy individuals, inter-individual differences in brain anatomy significantly influence current distribution during tDCS, an effect that might be aggravated by variations in cortical atrophy in AD patients. OBJECTIVE: To measure the effect of individualized HD-tDCS in AD patients. METHODS: Nineteen AD patients were randomly assigned to receive active or sham high-definition tDCS (HD-tDCS). Computational modeling of the HD-tDCS-induced electric field in each patient's brain was analyzed based on magnetic resonance imaging (MRI) scans. The chosen montage provided the highest net anodal electric field in the left dorsolateral prefrontal cortex (DLPFC). An accelerated HD-tDCS design was conducted (2 mA for 3×20 min) on two separate days. Pre- and post-intervention cognitive tests and T1 and T2-weighted MRI and diffusion tensor imaging data at baseline were analyzed. RESULTS: Different montages were optimal for individual patients. The active HD-tDCS group improved significantly in delayed memory and MMSE performance compared to the sham group. Five participants in the active group had higher scores on delayed memory post HD-tDCS, four remained stable and one declined. The active HD-tDCS group had a significant positive correlation between fractional anisotropy in the anterior thalamic radiation and delayed memory score. CONCLUSION: HD-tDCS significantly improved delayed memory in AD. Our study can be regarded as a proof-of-concept attempt to increase tDCS efficacy. The present findings should be confirmed in larger samples.

What does hand motor function tell us about our aging brain in association with WMH?

BACKGROUND: White matter hyperintensities (WMH) are a common cerebral finding in older people. WMH are usually asymptomatic, but excessive WMH are associated with cognitive decline and dementia. WMH are also among the neurological findings most consistently associated with declining motor performance in healthy ageing. AIMS: To determine if WMH load is associated with simple and complex motor movements in dominant and non-dominant hands in cognitively intact older subjects. METHODS: Hand motor performance was assessed with the Purdue Pegboard and Finger-tapping tests on 44 healthy right-handed participants, mean age 70.9 years (range 59-84 years). Participants also underwent magnetic resonance (MR) imaging, which were used to quantify WMH volume. The effect of WMH on the motor parameters was assessed via mediation analyses. RESULTS: WMH load increased significantly with age, while the motor scores decreased significantly with age. WMH load mediated only the relationship between age and left-hand pegboard scores. DISCUSSION: WMH mediated only the more complex Purdue Pegboard task for the non-dominant hand. This is likely because complex movements in the non-dominant hand recruit a larger cerebral network, which is more vulnerable to WMH. CONCLUSIONS: Complex hand movements in the non-dominant hand are mediated by WMH. Subtle loss of motor movements of non-dominant hand might predict future excessive white matter atrophy.

The effect of white matter hyperintensities on regional brain volumes and white matter microstructure, a population-based study in HUNT.

Even though age-related white matter hyperintensities (WMH) begin to emerge in middle age, their effect on brain micro- and macrostructure in this age group is not fully elucidated. We have examined how presence of WMH and load of WMH affect regional brain volumes and microstructure in a validated, representative general population sample of 873 individuals between 50 and 66 years. Presence of WMH was determined as Fazakas grade ≥1. WMH load was WMH volume from manual tracing of WMHs divided on intracranial volume. The impact of age appropriate WMH (Fazakas grade 1) on the brain was also investigated. Major novel findings were that even the age appropriate WMH group had widespread macro- and microstructural changes in gray and white matter, showing that the mere presence of WMH, not just WMH load is an important clinical indicator of brain health. With increasing WMH load, structural changes spread centrifugally. Further, we found three major patterns of FA and MD changes related to increasing WMH load, demonstrating a heterogeneous effect on white matter microstructure, where distinct patterns were found in the proximity of the lesions, in deep white matter and in white matter near the cortex. This study also raises several questions about the onset of WMH related pathology, in particular, whether some of the aberrant brain structural and microstructural findings are present before the emergence of WMH. We also found, similar to other studies, that WMH risk factors had low explanatory power for WMH, making it unclear which factors lead to WMH.

Neuroanatomical correlates of verbal fluency in early Alzheimer's disease and normal aging.

Verbal fluency (VF) impairments occur early in Alzheimer's disease (AD) and to a lesser extent also in normal aging. However, the neural underpinnings of these impairments are not fully understood. The present study evaluated whether VF impairments in early AD and normal aging rely upon common or different neuroanatomical correlates. We examined the association between VF performance and brain structure in 18 mild AD patients and 24 healthy elderly. Linear regressions were performed between accuracy and time intervals in VF scores and structural measurements of cerebral gray matter (GM) and white matter (WM) using MRI. Results showed that semantic VF correlated exclusively with GM in cerebellum, left temporal fusiform cortex, and WM in uncinate fasciculus, inferior fronto-occipital fasciculus and corpus callosum. Phonemic VF showed unique associations between intervals and WM in left-hemisphere tracts. The association between GM in hippocampus, subcortical structures and semantic accuracy differentiated patients from controls. Results showed that VF impairments are primarily associated with same structural brain changes in AD as in healthy elderly but at exaggerated levels. However, specific VF deficiencies and their underlying neural correlates exist and these clearly differentiate the initial stages of AD.

Visual function and white matter microstructure in very-low-birth-weight (VLBW) adolescents--a DTI study.

Premature birth is associated with visual impairments, due to both cerebral and ocular pathology. This study examined the relationship between cerebral white matter microstructure, evaluated by diffusion tensor imaging (DTI), and visual function, in 30 preterm born adolescents with very low birth weight (VLBW=birth weight⩽1500g) and an age-matched group of 45 term born controls. Visual acuity correlated positively with fractional anisotropy (FA) in corpus callosum and in frontal white matter areas in the VLBW participants, but not in the control participants. Callosal visual connections may play a more important role in the development of good visual acuity than previously acknowledged in preterm born children.