The role of the thalamus and hippocampus in episodic memory performance in patients with multiple sclerosis.

BACKGROUND: Episodic memory loss is one of the most common cognitive symptoms in patients with multiple sclerosis (MS), but the pathophysiology of this symptom remains unclear. Both the hippocampus and thalamus have been implicated in episodic memory and show regional atrophy in patients with MS. OBJECTIVE: In this work, we used functional magnetic resonance imaging (fMRI) during a verbal episodic memory task, lesion load, and volumetric measures of the hippocampus and thalamus to assess the relative contributions to verbal and visual-spatial episodic memory. METHODS: Functional activation, lesion load, and volumetric measures from 32 patients with MS and 16 healthy controls were used in a predictive analysis of episodic memory function. RESULTS: After adjusting for disease duration, immediate recall performance on a visual-spatial episodic memory task was significantly predicted by hippocampal volume ( p < 0.003). Delayed recall on the same task was significantly predicted by volume of the left thalamus ( p < 0.003). For both memory measures, functional activation of the thalamus during encoding was more predictive than that of volume measures ( p < 0.002). CONCLUSION: Our results suggest that functional activation may be useful as a predictive measure of episodic memory loss in patients with MS.

Activation volume vs BOLD signal change as measures of fMRI activation - Its impact on GABA - fMRI activation correlation.

PURPOSE: To explore the relative robustness of functional MRI (fMRI) activation volume and blood oxygen level-dependent (BOLD) signal change as fMRI metric, and to study the effect of relative robustness on the correlation between fMRI activation and cortical gamma amino butyric acid (GABA) in healthy controls and patients with multiple sclerosis (MS). METHODS: fMRI data were acquired from healthy controls and patients with MS, with the subjects peforming self paced bilateral finger tapping in block design. GABA spectroscopy was performed with voxel placed on the area of maximum activation during fMRI. Activation volume and BOLD signal changes at primary motor cortex (M1), as well as GABA concentration were calculated for each patient. RESULTS: Activation volume correlated with BOLD signal change in healthy controls, but no such correlation was observed in patients with MS. This difference was likely the result of higher intersubject noise variance in the patient population. GABA concentration correlated with M1 activation volume in patients but not in controls, and did not correlate with any fMRI metric in patients or controls. CONCLUSION: Our data suggest that activation volume is a more robust measure than BOLD signal change in a group with high intersubject noise variance as in patients with MS. Additionally, this study demonstrated difference in correlation behavior between GABA concentration and the 2 fMRI metrics in patients with MS, suggesting that GABA - activation volume correlation is more appropriate measure in the patient group.

Exercise Therapy for Parkinson's Disease: Pedaling Rate Is Related to Changes in Motor Connectivity.

Forced-rate lower-extremity exercise has recently emerged as a potential safe and low-cost therapy for Parkinson's disease (PD). The efficacy is believed to be dependent on pedaling rate, with rates above the subjects' voluntary exercise rates being most beneficial. In this study, we use functional connectivity magnetic resonance imaging (MRI) to further elucidate the mechanism underlying this effect. Twenty-seven PD patients were randomized to complete 8 weeks of forced-rate exercise (FE) or voluntary-rate exercise (VE). Exercise was delivered using a specialized stationary bicycle, which can augment patients' voluntary exercise rates. The FE group received assistance from the cycle. Imaging was conducted at baseline, end of therapy, and after 4 weeks of follow-up. Functional connectivity (FC) was determined via seed-based correlation analysis, using activation-based seeds in the primary motor cortex (M1). The change in FC after exercise was compared using linear correlation with pedaling rate. Results of the correlation analysis showed a strong positive correlation between pedaling rate and change in FC from the most affected M1 to the ipsilateral thalamus. This effect persisted after 4 weeks of follow-up. These results indicate that a plausible mechanism for the therapeutic efficacy of high-rate exercise in PD is that it improves thalamo-cortical connectivity.

Repeated head trauma is associated with smaller thalamic volumes and slower processing speed: the Professional Fighters' Brain Health Study.

OBJECTIVES: Cumulative head trauma may alter brain structure and function. We explored the relationship between exposure variables, cognition and MRI brain structural measures in a cohort of professional combatants. METHODS: 224 fighters (131 mixed martial arts fighters and 93 boxers) participating in the Professional Fighters Brain Health Study, a longitudinal cohort study of licensed professional combatants, were recruited, as were 22 controls. Each participant underwent computerised cognitive testing and volumetric brain MRI. Fighting history including years of fighting and fights per year was obtained from self-report and published records. Statistical analyses of the baseline evaluations were applied cross-sectionally to determine the relationship between fight exposure variables and volumes of the hippocampus, amygdala, thalamus, caudate, putamen. Moreover, the relationship between exposure and brain volumes with cognitive function was assessed. RESULTS: Increasing exposure to repetitive head trauma measured by number of professional fights, years of fighting, or a Fight Exposure Score (FES) was associated with lower brain volumes, particularly the thalamus and caudate. In addition, speed of processing decreased with decreased thalamic volumes and with increasing fight exposure. Higher scores on a FES used to reflect exposure to repetitive head trauma were associated with greater likelihood of having cognitive impairment. CONCLUSIONS: Greater exposure to repetitive head trauma is associated with lower brain volumes and lower processing speed in active professional fighters.

The protective effect of education on cognition in professional fighters.

Education has a protective effect against cognitive deficits following various forms of brain insult. Professional fighting (boxing and mixed martial arts) provides a model for assessing the impact of cumulative brain injuries on cognition and brain health. In the current cross-sectional observational study, we explore whether education would be protective against cognitive loss in fighters. We tested 141 professional fighters using a computerized neurocognitive battery, in addition to structural MRI. We used automated segmentation software to compute the volumes of various brain structures. We found fighters with high school education or less to show more associations between fight exposure and cognitive test scores. The relationship between brain structure volume and exposure did not differ based on education. These results are interpreted as putatively showing a protective effect of education on functional integrity in fighters, although longitudinal data and a larger sample size are required to further understand this relationship.

Professional fighters brain health study: rationale and methods.

Repetitive head trauma is a risk factor for Alzheimer's disease and is the primary cause of chronic traumatic encephalopathy. However, little is known about the natural history of, and risk factors for, chronic traumatic encephalopathy or about means of early detection and intervention. The Professional Fighters Brain Health Study is a longitudinal study of active professional fighters (boxers and mixed martial artists), retired professional fighters, and controls matched for age and level of education. The main objective of the Professional Fighters Brain Health Study is to determine the relationships between measures of head trauma exposure and other potential modifiers and changes in brain imaging and neurological and behavioral function over time. The study is designed to extend over 5 years, and we anticipate enrollment of more than 400 boxers and mixed martial artists. Participants will undergo annual evaluations that include 3-tesla magnetic resonance imaging scanning, computerized cognitive assessments, speech analysis, surveys of mood and impulsivity, and blood sampling for genotyping and exploratory biomarker studies. Statistical models will be developed and validated to predict early and progressive changes in brain structure and function. A composite fight exposure index, developed as a summary measure of cumulative traumatic exposure, shows promise as a predictor of brain volumes and cognitive function.

In vivo magnetic resonance spectroscopy measurement of gray-matter and white-matter gamma-aminobutyric acid concentration in sensorimotor cortex using a motion-controlled MEGA point-resolved spectroscopy sequence.

Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter in the brain. Understanding the GABA concentration, in vivo, is important to understand normal brain function. Using MEGA point-resolved spectroscopy sequence with interleaved water scans to detect subject motion, GABA level of sensorimotor cortex was measured using a voxel identified from a functional magnetic resonance imaging scan. The GABA level in a 20×20×20-mm(3) voxel consisting of 37%±7% gray matter, 52%±12% white matter and 11%±8% cerebrospinal fluid in the sensorimotor region was measured to be 1.43±0.48 mM. In addition, using linear regression analysis, GABA concentrations within gray and white matter were calculated to be 2.87±0.61 and 0.33±0.11 mM, respectively.

Hemispheric asymmetries in phonological processing of tones versus segmental units.

The aim of this functional magnetic resonance imaging study is to identify neuroanatomical substrates underlying phonological processing of segmental (consonant, rhyme) and suprasegmental (tone) units. An auditory verbal recognition paradigm was used in which native speakers of Mandarin Chinese were required to match a phonological unit that occurs in a list of three syllables to the corresponding unit of a following probe. The results show that hemispheric asymmetries arise depending on the type of phonological unit. In direct contrasts between phonological units, tones, relative to consonants and rhymes, yield increased activation in frontoparietal areas of the right hemisphere. This finding indicates that the cortical circuitry subserving lexical tones differs from that of consonants or rhymes.

Val-407 and Ile-408 in the beta5'-loop of pancreatic lipase mediate lipase-colipase interactions in the presence of bile salt micelles.

In a previous study, we demonstrated that the beta5'-loop in the C-terminal domain of human pancreatic triglyceride lipase (hPTL) makes a major contribution in the function of hPTL (Chahinian et al. (2002) Biochemistry 41, 13725-13735). In the present study, we characterized the contribution of three residues in the beta5'-loop, Val-407, Ile-408, and Leu-412, to the function of hPTL. By substituting charged residues, aspartate or lysine, in these positions, we altered the hydrophilic to lipophilic ratio of the beta5'-loop. Each of the mutants was expressed, purified, and characterized for activity and binding with both monolayers and emulsions and for binding to colipase. Experiments with monolayers and with emulsions suggested that the interaction of hPTL with a phospholipid monolayer differs from the interaction of the hPTL-colipase complex with a dicaprin monolayer or a triglyceride emulsion (i.e. neutral lipids). Val-407, Ile-408, and Leu-412 make major contributions to interactions with monolayers, whereas only Val-407 and Ile-408 appear essential for activity on triglyceride emulsions in the presence of bile salt micelles. In solutions of taurodeoxycholate at micellar concentrations, a major effect of the beta5'-loop mutations is to change the interaction between hPTL and colipase. These observations support a major contribution of residues in the beta5'-loop in the function of hPTL and suggest that a third partner, bile salt micelles or the lipid interface or both, influence the binding of colipase and hPTL through interactions with the beta5'-loop.

Activation of the left planum temporale in pitch processing is shaped by language experience.

Implicit, abstract knowledge acquired through language experience can alter cortical processing of complex auditory signals. To isolate prelexical processing of linguistic tones (i.e., pitch variations that convey part of word meaning), a novel design was used in which hybrid stimuli were created by superimposing Thai tones onto Chinese syllables (tonal chimeras) and Chinese tones onto the same syllables (Chinese words). Native speakers of tone languages (Chinese, Thai) underwent fMRI scans as they judged tones from both stimulus sets. In a comparison of native vs. non-native tones, overlapping activity was identified in the left planum temporale (PT). In this area a double dissociation between language experience and neural representation of pitch occurred such that stronger activity was elicited in response to native as compared to non-native tones. This finding suggests that cortical processing of pitch information can be shaped by language experience and, moreover, that lateralized PT activation can be driven by top-down cognitive processing.

Selective attention to lexical tones recruits left dorsal frontoparietal network.

Phonological processing activates a posterior superior region of inferior prefrontal cortex, but questions still remain about the relationship between phonology and this particular region. In this fMRI experiment, subjects were asked to match an intrasyllabic unit (Chinese tones) in an experimental condition vs. whole syllables in a control condition. The only difference between conditions is mediated by focus of attention, either to a subpart (i.e. tone) of the syllable or to the whole syllable itself. Phonetic extraction of Chinese tones reveals a dorsal frontoparietal network in the LH that engages selective attention and internal guidance, two mediational components that are not restricted to phonological processing.