Natural biological variation of white matter microstructure is accentuated in Huntington's disease.

Huntington's disease (HD) is a monogenic neurodegenerative disorder caused by a CAG-repeat expansion in the Huntingtin gene. Presence of this expansion signifies certainty of disease onset, but only partly explains age at which onset occurs. Genome-wide association studies have shown that naturally occurring genetic variability influences HD pathogenesis and disease onset. Investigating the influence of biological traits in the normal population, such as variability in white matter properties, on HD pathogenesis could provide a complementary approach to understanding disease modification. We have previously shown that while white matter diffusivity patterns in the left sensorimotor network were similar in controls and HD gene-carriers, they were more extreme in the HD group. We hypothesized that the influence of natural variation in diffusivity on effects of HD pathogenesis on white matter is not limited to the sensorimotor network but extends to cognitive, limbic, and visual networks. Using tractography, we investigated 32 bilateral pathways within HD-related networks, including motor, cognitive, and limbic, and examined diffusivity metrics using principal components analysis. We identified three independent patterns of diffusivity common to controls and HD gene-carriers that predicted HD status. The first pattern involved almost all tracts, the second was limited to sensorimotor tracts, and the third encompassed cognitive network tracts. Each diffusivity pattern was associated with network specific performance. The consistency in diffusivity patterns across both groups coupled with their association with disease status and task performance indicates that naturally-occurring patterns of diffusivity can become accentuated in the presence of the HD gene mutation to influence clinical brain function.

Corpus callosal atrophy in premanifest and early Huntington's disease.

BACKGROUND: Volumetric MRI studies have highlighted the pronounced loss of white matter in premanifest and early Huntington's Disease (HD). The current study focussed on the corpus callosum (CC) since it provides interhemispheric connections to vulnerable cortical areas. OBJECTIVES: To investigate cross-sectional and longitudinal group differences in CC volume and hypothesis-driven associations with three cognitive tasks. METHODS: Baseline and 24-month 3T MRI were analysed from 106 premanifest (PreHD), (59 preHD-A ≥10.8 and 47 preHD-B <10.8 years from predicted onset), 84 early HD (53 Stage 1 (HD1) and 31 Stage 2 (HD2)) and 101 control subjects from the TRACK-HD study, using a semi-automated technique for CC delineation. Between-group differences in volume and 24-month atrophy rates, and correlations with cognitive performance were investigated using regression models, adjusting for potential confounders. RESULTS: PreHD-B, HD1 and HD2 had statistically significantly smaller baseline CC volumes (p < 0.001) and all groups had elevated 24-month atrophy rates compared with controls (p < 0.001). Smaller baseline CC volume was associated with impaired performance in the Circle Tracing Indirect task in early HD (p < 0.05). Positive, non-statistically significant relationships with Stroop Word Reading were shown in both gene-positive groups. There was no evidence of an association with the Trail Making B task. CONCLUSIONS: We found reduced CC volume and elevated 24-month atrophy rates, even in individuals far from disease onset. Structural degeneration of interhemispheric connections may contribute to cognitive deficits, such as performance in the Circle Tracing Indirect task in HD. Examination of different image acquisitions may provide more specific information about underlying CC degeneration.

Evaluation of multi-modal, multi-site neuroimaging measures in Huntington's disease: Baseline results from the PADDINGTON study.

BACKGROUND: Macro- and micro-structural neuroimaging measures provide valuable information on the pathophysiology of Huntington's disease (HD) and are proposed as biomarkers. Despite theoretical advantages of microstructural measures in terms of sensitivity to pathology, there is little evidence directly comparing the two. METHODS: 40 controls and 61 early HD subjects underwent 3 T MRI (T1- and diffusion-weighted), as part of the PADDINGTON study. Macrostructural volumetrics were obtained for the whole brain, caudate, putamen, corpus callosum (CC) and ventricles. Microstructural diffusion metrics of fractional anisotropy (FA), mean-, radial- and axial-diffusivity (MD, RD, AD) were computed for white matter (WM), CC, caudate and putamen. Group differences were examined adjusting for age, gender and site. A formal comparison of effect sizes determined which modality and metrics provided a statistically significant advantage over others. RESULTS: Macrostructural measures showed decreased regional and global volume in HD (p < 0.001); except the ventricles which were enlarged (p < 0.01). In HD, FA was increased in the deep grey-matter structures (p < 0.001), and decreased in the WM (CC, p = 0.035; WM, p = 0.053); diffusivity metrics (MD, RD, AD) were increased for all brain regions (p < 0.001). The largest effect sizes were for putamen volume, caudate volume and putamen diffusivity (AD, RD and MD); each was significantly larger than those for all other metrics (p < 0.05). CONCLUSION: The highest performing macro- and micro-structural metrics had similar sensitivity to HD pathology quantified via effect sizes. Region-of-interest may be more important than imaging modality, with deep grey-matter regions outperforming the CC and global measures, for both volume and diffusivity. FA appears to be relatively insensitive to disease effects.

The wandering mind of men: ERP evidence for gender differences in attention bias towards attractive opposite sex faces.

To examine the time course and automaticity of our attention bias towards attractive opposite sex faces, event-related potentials (ERPs) were recorded from 20 males and 20 females while they carried out a covert orienting task. Faces that were high, low or average in attractiveness, were presented in focus of attention, but were unrelated to task goals. Across the entire sample larger P2 amplitudes were found in response to both attractive and unattractive opposite sex faces, presumably reflecting early implicit selective attention to distinctive faces. In male but not female participants this was followed by an increased late slow wave for the attractive faces, signifying heightened processing linked to motivated attention. This latter finding is consistent with sexual strategy theory, which suggests that men and women have evolved to pursue different mating strategies with men being more attentive to cues such as facial beauty. In general, our ERP results suggest that, in addition to threat-related stimuli, other evolutionary-relevant information is also prioritized by our attention systems.

P50 sensory gating and attentional performance.

Sensory gating refers to the preattentional filtering of irrelevant sensory stimuli. This process may be impaired in schizotypy, which is a trait also associated with cigarette smoking. This association may in part stem from the positive effects of smoking on sensory gating and attention. The relationship among sensory gating, smoking, schizotypy and attention was examined in 39 undergraduates. Sensory gating was indexed by the P50 suppression paradigm, and attention was measured by the Attention Network Test (ANT) and a Stroop task. Results showed sensory gating to be positively correlated with performances on ANT and Stroop reflected in better alerting, less conflict between stimuli, faster reaction time, and greater accuracy. Smokers showed a pattern of a greater number of significant correlations between sensory gating and attention in comparison to non-smokers, although the relationship between sensory gating and attention was not affected by schizotypy. The majority of significant correlations were found in the region surrounding Cz. These findings are discussed relative to the potential modifying influence of smoking and schizotypy on sensory gating and attention.

Early and late auditory sensory gating: moderating influences from schizotypal personality, tobacco smoking status, and acute smoking.

Early (P50) and late (P200) auditory sensory gating were assessed in low and high schizotypal personality groups using Raine's Schizotypal Personality Questionnaire. We also assessed the impact of smoking as it relates to low and high schizotypal personalities. Low and high schizoptypal personality groups were divided into subgroups of participants who either smoked or did not smoke tobacco cigarettes. Participants were 39 (18 men) right-handed undergraduates. Using a paired-tone paradigm (40 pairs, 70 dB, 1000 Hz), smokers were tested while abstaining from smoking, and 5 min after smoking. Non-smokers were tested similarly without smoking. Midline and hemispheric sites were evaluated at frontal (F3/Fz/F4), fronto-central (FC3/FCz/FC4), central (C3/Cz/C4), centro-parietal (CP3/CPz/CP4), and parietal (P3/Pz/P4) regions. P50 sensory gating was better at midline sites than left/right hemispheric sites, whereas there was no difference in activation with respect to location for P200 sensory gating. Cz had better P50 sensory gating than other midline regions, whereas Fz, FCz and Cz had better P200 sensory gating than CPz and Pz. Hemispheric comparisons were made. At the central region for non-smokers, high schizotypys showed poorer P50 sensory gating than low schizotypys. Among low schizotypys, smokers showed poorer P50 sensory gating than non-smokers at the fronto-central and central regions smokers showed better P200 sensory gating than non-smokers at the central region. Smoking had no acute impact on either early (P50) or late (P200) sensory gating. Our data support the notion that early sensory gating and late sensory gating represent different sensory gating mechanisms with respect to low and high schizotypy personalities. Individual differences in early and late sensory gating need further investigation.

P50 sensory gating: impact of high vs. low schizotypal personality and smoking status.

Sensory gating deficits are seen in individuals with schizophrenia and schizotypal disorders, yet smoking influence, regional or lateral difference effects are rarely assessed. We examined sensory gating in smokers and non-smokers within university-level high and low schizotypal personality (HiS and LoS) groups using [Raine, A., 1991. The Schizotypal Personality Questionnaire (SPQ): A measure of schizotypal personality based on DSM-III-R criteria. Schizophr. Bull. 17, 555-564] Schizotypal Personality Questionnaire. Among 39 (18 men; 19 smokers) right-handed undergraduates, a paired-tone paradigm (40 pairs; 10 s ISI; 70 dB, 1000 Hz) was presented in two conditions (smokers while abstaining and after smoking). Sensory gating [S2(P50-N40)/S1(P50-N40)] was assessed at frontal, fronto-central, central, centro-parietal, and parietal midline and lateralized sites. Sensory gating was better at (1) midline than left/right hemispheric sites, and (2) fronto-central and central midline sites. At fronto-central/central lateral sites, (1) among non-smokers, better sensory gating occurred in LoS than HiS, (2) among smokers, better sensory gating occurred in HiS than LoS, and (3) among LoSs, smokers showed less sensory gating than non-smokers. No acute smoking effects emerged. Unlike schizophrenia studies, smoking did not impact sensory gating. Differences among smokers and non-smokers in LoS and HiS groups reinforce need to evaluate both smoking and schizotypal characteristics, as well as midline and lateral sites in anterior to posterior regions, in sensory gating studies.

Increased anterior corpus callosum size associated positively with hypnotizability and the ability to control pain.

This is the first MRI study to report differences in brain structure size between low and highly hypnotizable, healthy, right-handed young adults. Participants were stringently screened for hypnotic susceptibility with two standardized scales, and then exposed to hypnotic analgesia training to control cold pressor pain. Only the highly hypnotizable subjects (HHs) who eliminated pain perception were included in the present study. These HHs, who demonstrated more effective attentional and inhibitory capabilities, had a significantly (P < 0.003) larger (31.8%) rostrum, a corpus callosum area involved in the allocation of attention and transfer of information between prefrontal cortices, than low hypnotizable subjects (LHs). These results provide support to the neuropsychophysiological model that HHs have more effective frontal attentional systems implementing control, monitoring performance and inhibiting unwanted stimuli from conscious awareness, than LHs.

Hypnotic susceptibility: multidimensional relationships with Cloninger's Tridimensional Personality Questionnaire, COMT polymorphisms, absorption, and attentional characteristics.

One hundred and seven healthy volunteers were administered Cloninger's Tridimensional Personality Questionnaire (TPQ), the Differential Attentional Processes Inventory (DAPI), the Tellegen Absorption Scale (TAS), and the Stanford Hypnotic Susceptibility Scale, Form C (SHSS:C). Polymorphisms of catechol O-methyltransferase (COMT), an enzyme involved in dopamine metabolism, were assessed. Highly hypnotizable subjects self-reported greater TPQ persistence, absorption, and focused attentional abilities. Hierarchical multiple regression analyses found that TPQ persistence, COMT, TAS, and the DAPI attentional scales explained 43.8% of the variance in women and 29% in men. Membership was correctly discriminated for the more extreme low (62.1%) and highly (81.5%) hypnotizable groups. These results suggest that highly hypnotizable persons have a more effective frontolimbic attentional system and further suggest the involvement of dopaminergic systems in hypnotizability.

Spatial summation of pain processing in the human brain as assessed by cerebral event related potentials.

To understand spatial summation of pain processing in the brain, we investigated the cerebral evoked responses to non-painful and painful contact heat stimulation (70 degrees C/s fast onset; intensity 2,4,6, corresponding to the individual's non-, slight and moderate pain) comparing one (1s) vs. two spots (2s) in 11 subjects while electroencephalographic signals were recorded. Significant spatial summation effects were shown only for the pain levels. For moderate pain, global field power examination isolated two peak activations for the vertex (Cz) N550 and P750 components. The single dipole modelling identified as likely the supplementary motor area, SMA area-6 source for N550, and posterior cingulate area-23 for P750. These source components showed a significantly faster (41.2 ms) latency and a shift in location from dorsal to ventral SMA of N550 toward cingulate area-31 between the 1s and 2s conditions. The temporal and spatial shift during spatial summation may reflect speeding up of the limbic affective reaction and prefrontal cognitive preparation in impending aversion and is deemed essential for integration of bodily sensations, such as pain.

Enhancement of auditory sensory gating and stimulus-bound gamma band (40 Hz) oscillations in heavy tobacco smokers.

The effects of smoking tobacco on sensory gating, P50 and stimulus-bound gamma band oscillations (GBO; 32-48 Hz) in auditory evoked potentials were examined in a paired-tone paradigm (50 tone pip pairs; 70 dB, 1000 Hz). Thirteen cigarette (20+/day) smokers were tested after abstaining overnight and after smoking; 13 age-matched never-smokers were tested twice. Smokers exhibited chronic (rather than acute) effects in the frontal region: (1) larger P50 and GBO responses; (2) greater P50 and GBO sensory gating suppression. GBO analyses showed earlier sensory gating in smokers. These chronic effects of greater cortical activation and sensory gating may reflect persistent dopaminergic activation due to the inhibition of monoamine oxidase observed in smokers.

Enhanced visual memory during hypnosis as mediated by hypnotic responsiveness and cognitive strategies.

To investigate the hypothesis that hypnosis has an enhancing effect on imagery processing, as mediated by hypnotic responsiveness and cognitive strategies, four experiments compared performance of low and high, or low, medium, and high, hypnotically responsive subjects in waking and hypnosis conditions on a successive visual memory discrimination task that required detecting differences between successively presented picture pairs in which one member of the pair was slightly altered. Consistently, hypnotically responsive individuals showed enhanced performance during hypnosis, whereas nonresponsive ones did not. Hypnotic responsiveness correlated .52 (p less than .001) with enhanced performance during hypnosis, but it was uncorrelated with waking performance (Experiment 3). Reaction time was not affected by hypnosis, although high hypnotizables were faster than lows in their responses (Experiments 1 and 2). Subjects reported enhanced imagery vividness on the self-report Vividness of Visual Imagery Questionnaire during hypnosis. The differential effect between lows and highs was in the anticipated direction but not significant (Experiments 1 and 2). As anticipated, hypnosis had no significant effect on a discrimination task that required determining whether there were differences between pairs of simultaneously presented pictures. Two cognitive strategies that appeared to mediate visual memory performance were reported: (a) detail strategy, which involved the memorization and rehearsal of individual details for memory, and (b) holistic strategy, which involved looking at and remembering the whole picture with accompanying imagery. Both lows and highs reported similar predominantly detail-oriented strategies during waking; only highs shifted to a significantly more holistic strategy during hypnosis. These findings suggest that high hypnotizables have a greater capacity for cognitive flexibility (Batting, 1979) than do lows. Results are discussed in terms of several theoretical approaches: Paivio's (1971) dual-coding theory and Craik and Tulving's (1975) depth of processing theory. Additional discussion is given to the question of whether hypnosis involves a shift in cerebral dominance, as reflected by the cognitive strategy changes and enhanced imagery processing.