The neurological underpinnings of cluttering: Some initial findings

Background Cluttering is a fluency disorder characterised by overly rapid or jerky speech patterns that compromise intelligibility. The neural correlates of cluttering are unknown but theoretical accounts implicate the basal ganglia and medial prefrontal cortex. Dysfunction in these brain areas would be consistent with difficulties in selection and control of speech motor programs that are characteristic of speech disfluencies in cluttering. There is a surprising lack of investigation into this disorder using modern imaging techniques. Here, we used functional MRI to investigate the neural correlates of cluttering. Method We scanned 17 adults who clutter and 17 normally fluent control speakers matched for age and sex. Brain activity was recorded using sparse-sampling functional MRI while participants viewed scenes and either (i) produced overt speech describing the scene or (ii) read out loud a sentence provided that described the scene. Speech was recorded and analysed off line. Differences in brain activity for each condition compared to a silent resting baseline and between conditions were analysed for each group separately (cluster-forming threshold Z > 3.1, extent p 30 voxels, uncorrected). Results In both conditions, the patterns of activation in adults who clutter and control speakers were strikingly similar, particularly at the cortical level. Direct group comparisons revealed greater activity in adults who clutter compared to control speakers in the lateral premotor cortex bilaterally and, as predicted, on the medial surface (pre-supplementary motor area). Subcortically, adults who clutter showed greater activity than control speakers in the basal ganglia. Specifically, the caudate nucleus and putamen were overactive in adults who clutter for the comparison of picture description with sentence reading. In addition, adults who clutter had reduced activity relative to control speakers in the lateral anterior cerebellum bilaterally. Eleven of the 17 adults who clutter also stuttered. This comorbid diagnosis of stuttering was found to contribute to the abnormal overactivity seen in the group of adults who clutter in the right ventral premotor cortex and right anterior cingulate cortex. In the remaining areas of abnormal activity seen in adults who clutter compared to controls, the subgroup who clutter and stutter did not differ from the subgroup who clutter but do not stutter. Conclusions Our findings were in good agreement with theoretical predictions regarding the neural correlates of cluttering. We found evidence for abnormal function in the basal ganglia and their cortical output target, the medial prefrontal cortex. The findings are discussed in relation to models of cluttering that point to problems with motor control of speech

Separation of trait and state in stuttering

Stuttering is a disorder in which the smooth flow of speech is interrupted. People who stutter show structural and functional abnormalities in the speech and motor system. It is unclear whether functional differences reflect general traits of the disorder or are specifically related to the dysfluent speech state. We used a hierarchical approach to separate state and trait effects within stuttering. We collected sparse‐sampled functional MRI during two overt speech tasks (sentence reading and picture description) in 17 people who stutter and 16 fluent controls. Separate analyses identified indicators of: (1) general traits of people who stutter; (2) frequency of dysfluent speech states in subgroups of people who stutter; and (3) the differences between fluent and dysfluent states in people who stutter. We found that reduced activation of left auditory cortex, inferior frontal cortex bilaterally, and medial cerebellum were general traits that distinguished fluent speech in people who stutter from that of controls. The stuttering subgroup with higher frequency of dysfluent states during scanning (n = 9) had reduced activation in the right subcortical grey matter, left temporo‐occipital cortex, the cingulate cortex, and medial parieto‐occipital cortex relative to the subgroup who were more fluent (n = 8). Finally, during dysfluent states relative to fluent ones, there was greater activation of inferior frontal and premotor cortex extending into the frontal operculum, bilaterally. The above differences were seen across both tasks. Subcortical state effects differed according to the task. Overall, our data emphasise the independence of trait and state effects in stuttering

Regular smoking of male ancestors in adolescence and fat mass in young adult grandchildren and great-grandchildren

Background: Previous studies using the Avon Longitudinal Study of Parents and Children (ALSPAC) have shown that if men commenced smoking prior to the onset of puberty their sons, their granddaughters and great-granddaughters were more likely to have excess fat (but not lean) mass during childhood, adolescence and early adulthood. In this study we assess associations between ancestral smoking during adolescence (ages 11–16 years) with fat and lean mass of subsequent generations at two ages. Methods: We analysed data on exposures of grandparents and great-grandparents collected by ALSPAC. The outcomes were the fat masses of their grandchildren and great-grandchildren measured at ages 17 and 24. Measures of lean mass were used as controls. Adjustment was made for 8–10 demographic factors using multiple regression. Results: We found associations between adolescent smoking of the paternal grandfathers and the adjusted fat mass of their grandchildren, but no associations with the grandchildren’s lean mass. Grandchildren at age 17 had an average excess fat mass of +1.65 [95% CI +0.04, +3.26] Kg, and at age 24 an average excess of +1.55 [95% CI -0.27, +3.38] Kg. Adolescent smoking by the maternal grandfather showed similar, but weaker, associations: at 17 an average excess fat mass of +1.02 Kg [95% CI -0.20, +2.25] Kg, and at 24 an average excess of +1.28 [95% CI -0.11, +2.66] Kg. There were no pronounced differences between the sexes of the children. For the great-grandparents there were few convincing results, although numbers were small. Conclusions: We have shown associations between grandfathers’ smoking in adolescence and increased fat (but not lean) mass in their children. Confirmation of these associations is required, either in a further data set or by demonstrating the presence of supportive biomarkers

Human transgenerational observations of regular smoking before puberty on fat mass in grandchildren and great-grandchildren

Previously, using data from the Avon Longitudinal Study of Parents and Children (ALSPAC) we showed that sons of fathers who had started smoking regularly before puberty (< 13 years) had increased fat mass during childhood, adolescence, and early adulthood. We now show that if the paternal grandfather had started smoking pre-puberty, compared with later in childhood (13–16 years), his granddaughters, but not grandsons, had evidence of excess fat mass at two ages: mean difference + 3.54 kg; (P with 1-tailed test) = 0.043 at 17 years, and + 5.49 kg; (P(1) = 0.016) at age 24. When fathers of maternal grandfathers had started smoking pre-puberty, their great-granddaughters, but not great-grandsons, had excess body fat: + 5.35 kg (P(1) = 0.050) at 17, and + 6.10 kg (P(1) = 0.053) at 24 years. Similar associations were not found with lean mass, in a sensitivity analysis. To determine whether these results were due to the later generations starting to smoke pre-puberty, further analyses omitted those in subsequent generations who had smoked regularly from < 13 years. The results were similar. If these associations are confirmed in another dataset or using biomarkers, this will be one of the first human demonstrations of transgenerational effects of an environmental exposure across four generations

Neocerebellar Crus I Abnormalities Associated with a Speech and Language Disorder Due to a Mutation in FOXP2

Bilateral volume reduction in the caudate nucleus has been established as a prominent brain abnormality associated with a FOXP2 mutation in affected members of the ‘KE family’, who present with developmental orofacial and verbal dyspraxia in conjunction with pervasive language deficits. Despite the gene’s early and prominent expression in the cerebellum and the evidence for reciprocal cerebellum-basal ganglia connectivity, very little is known about cerebellar abnormalities in affected KE members. Using cerebellum-specific voxel-based morphometry (VBM) and volumetry, we provide converging evidence from subsets of affected KE members scanned at three time points for grey matter (GM) volume reduction bilaterally in neocerebellar lobule VIIa Crus I compared with unaffected members and unrelated controls. We also show that right Crus I volume correlates with left and total caudate nucleus volumes in affected KE members, and that right and total Crus I volumes predict the performance of affected members in non-word repetition and non-verbal orofacial praxis. Crus I also shows bilateral hypo-activation in functional MRI in the affected KE members relative to controls during non-word repetition. The association of Crus I with key aspects of the behavioural phenotype of this FOXP2 point mutation is consistent with recent evidence of cerebellar involvement in complex motor sequencing. For the first time, specific cerebello-basal ganglia loops are implicated in the execution of complex oromotor sequences needed for human speech

The type VII secretion system protects Staphylococcus aureus against antimicrobial host fatty acids

The Staphylococcus aureus type VII secretion system (T7SS) exports several proteins that are pivotal for bacterial virulence. The mechanisms underlying T7SS-mediated staphylococcal survival during infection nevertheless remain unclear. Here we report that S. aureus lacking T7SS components are more susceptible to host-derived antimicrobial fatty acids. Unsaturated fatty acids such as linoleic acid (LA) elicited an increased inhibition of S. aureus mutants lacking T7SS effectors EsxC, EsxA and EsxB, or the membrane-bound ATPase EssC, compared to the wild-type (WT). T7SS mutants generated in different S. aureus strain backgrounds also displayed an increased sensitivity to LA. Analysis of bacterial membrane lipid profiles revealed that the esxC mutant was less able to incorporate LA into its membrane phospholipids. Although the ability to bind labelled LA did not differ between the WT and mutant strains, LA induced more cell membrane damage in the T7SS mutants compared to the WT. Furthermore, proteomic analyses of WT and mutant cell fractions revealed that, in addition to compromising membranes, T7SS defects induce oxidative stress and hamper their response to LA challenge. Thus, our findings indicate that T7SS contribute to maintaining S. aureus membrane integrity and homeostasis when bacteria encounter antimicrobial fatty acids

The neurological underpinnings of cluttering: Some initial findings

a b s t r a c t Background: Cluttering is a fluency disorder characterised by overly rapid or jerky speech patterns that compromise intelligibility. The neural correlates of cluttering are unknown but theoretical accounts implicate the basal ganglia and medial prefrontal cortex. Dysfunction in these brain areas would be consistent with difficulties in selection and control of speech motor programs that are characteristic of speech disfluencies in cluttering. There is a surprising lack of investigation into this disorder using modern imaging techniques. Here, we used functional MRI to investigate the neural correlates of cluttering. Method: We scanned 17 adults who clutter and 17 normally fluent control speakers matched for age and sex. Brain activity was recorded using sparse-sampling functional MRI while participants viewed scenes and either (i) produced overt speech describing the scene or (ii) read out loud a sentence provided that described the scene. Speech was recorded and analysed off line. Differences in brain activity for each condition compared to a silent resting baseline and between conditions were analysed for each group separately (cluster-forming threshold Z &gt; 3.1, extent p &lt; 0.05, corrected) and then these differences were further compared between the two groups (voxel threshold p &lt; 0.01, extent &gt; 30 voxels, uncorrected). Results: In both conditions, the patterns of activation in adults who clutter and control speakers were strikingly similar, particularly at the cortical level. Direct group comparisons revealed greater activity in adults who clutter compared to control speakers in the lateral premotor cortex bilaterally and, as predicted, on the medial surface (pre-supplementary motor area). Subcortically, adults who clutter showed greater activity than control speakers in the basal ganglia. Specifically, the caudate nucleus and putamen were overactive in adults who clutter for the comparison of picture description with sentence reading. In addition, adults who clutter had reduced activity relative to control speakers in the lateral anterior cerebellum bilaterally. Eleven of the 17 adults who clutter also stuttered. This comorbid diagnosis of stuttering was found to contribute to the abnormal overactivity seen in the group of adults who clutter in the right ventral premotor cortex and right anterior cingulate cortex. In the remaining areas of abnormal activity seen in adults who clutter compared to controls, the subgroup who clutter and stutter did not differ from the subgroup who clutter but do not stutter. Conclusions: Our findings were in good agreement with theoretical predictions regarding the neural correlates of cluttering. We found evidence for abnormal function in the basal ganglia and their cortical output target, the medial prefrontal cortex. The findings are discussed in relation to models of cluttering that point to problems with motor control of speech. Educational objectives: This paper reports findings on the neural correlates seen in adults who clutter, and offers hypotheses as to how these might map onto the behaviours seen amongst those who clutter. Readers will be able to (a) identify the structures that are implicated in the disorder of cluttering, (b) understand arguments relating these structures to the behavioural expression of the disorder, (c) understand some of the complexities in interpreting data pertaining to recovery from cluttering, (d) understand where future efforts in research into the neurological correlates of cluttering should be focussed

Facilitation of motor excitability during listening to spoken sentences is not modulated by noise or semantic coherence

Comprehending speech can be particularly challenging in a noisy environment and in the absence of semantic context. It has been proposed that the articulatory motor system would be recruited especially in difficult listening conditions. However, it remains unknown how signal-to-noise ratio (SNR) and semantic context affect the recruitment of the articulatory motor system when listening to continuous speech. The aim of the present study was to address the hypothesis that involvement of the articulatory motor cortex increases when the intelligibility and clarity of the spoken sentences decreases, because of noise and the lack of semantic context. We applied Transcranial Magnetic Stimulation (TMS) to the lip and hand representations in the primary motor cortex and measured motor evoked potentials from the lip and hand muscles, respectively, to evaluate motor excitability when young adults listened to sentences. In Experiment 1, we found that the excitability of the lip motor cortex was facilitated during listening to both semantically anomalous and coherent sentences in noise relative to non-speech baselines, but neither SNR nor semantic context modulated the facilitation. In Experiment 2, we replicated these findings and found no difference in the excitability of the lip motor cortex between sentences in noise and clear sentences without noise. Thus, our results show that the articulatory motor cortex is involved in speech processing even in optimal and ecologically valid listening conditions and that its involvement is not modulated by the intelligibility and clarity of speech