Auditory lexical decisions in children with specific language impairment

This study examined spoken-word recognition in children with specific language impairment (SLI) and normally developing children matched separately for age and receptive language ability. Accuracy and reaction times on an auditory lexical decision task were compared. Children with SLI were less accurate than both control groups. Two subgroups of children with SLI, distinguished by performance accuracy only, were identified. One group performed within normal limits, while a second group was significantly less accurate. Children with SLI were not slower than the age-matched controls or language-matched controls. Further, the time taken to detect an auditory signal, make a decision, or initiate a verbal response did not account for the differences between the groups. The findings are interpreted as evidence for language-appropriate processing skills acting upon imprecise or underspecified stored representations.

LGI1 mutations in temporal lobe epilepsies

Background and Objectives: A number of familial temporal lobe epilepsies (TLE) have been recently recognized. Mutations in LGI1 (leucine-rich, glioma-inactivated 1 gene) have been found in a few families with the syndrome of autosomal dominant partial epilepsy with auditory features (ADPEAF). The authors aimed to determine the spectrum of TLE phenotypes with LGI1 mutations, to study the frequency of mutations in ADPEAF, and to examine the role of LGI1 paralogs in ADPEAF without LGI1 mutations. Methods: The authors performed a clinical and molecular analysis on 75 pedigrees comprising 54 with a variety of familial epilepsies associated with TLE and 21 sporadic TLE cases. All were studied for mutations in LGI1. ADPEAF families negative for LGI1 mutations were screened for mutations in LGI2, LGI3, and LGI4. Results: Four families had ADPEAF, 22 had mesial TLE, 11 had TLE with febrile seizures, two had TLE with developmental abnormalities, and 15 had various other TLE syndromes. LGI1 mutations were found in two of four ADPEAF families, but in none of the other 50 families nor in the 21 individuals with sporadic TLE. The mutations were novel missense mutations in exons 1 (c. 124T --> G; C42G) and 8 (c. 1418C --> T; S473L). No mutations in LGI2, LGI3, or LGI4 were found in the other two ADPEAF families. Conclusion: In TLE, mutations in LGI1 are specific for ADPEAF but do not occur in all families. ADPEAF is genetically heterogeneous, but mutations in LGI2, LGI3, or LGI4 did not account for families without LGI1 mutations.

Familial partial epilepsy with variable foci: Clinical features and linkage to chromosome 22q12

Background: Familial partial epilepsy with variable foci (FPEVF) is an autosomal dominant syndrome characterized by partial seizures originating from different brain regions in different family members in the absence of detectable structural abnormalities. A gene for FPEVF was mapped to chromosome 22q12 in two distantly related French-Canadian families. Methods: We describe the clinical features and performed a linkage analysis in a Spanish kindred and in a third French-Canadian family distantly related to the original pedigrees. Results: Onset of seizures was typically in middle childhood, and attacks were usually easy to control. Seizure semiology varied among family members but was constant for each individual. In some, a pattern of nocturnal frontal lobe seizures led to consideration of the diagnosis of autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). The Spanish family was mapped to chromosome 22q (multipoint lod score, 3.4), and the new French-Canadian family had a multipoint lod score of 2.97 and shared the haplotype of the original French-Canadian families. Conclusions: Identification of the various forms of familial partial epilepsy is challenging, particularly in small families, in which insufficient individuals exist to identify a specific pattern. We provide clinical guidelines for this task, which will eventually be supplanted by specific molecular diagnosis. We confirmed linkage of FPEVF to chromosome 22q 12 and redefined the region to a 5.2-Mb segment of DNA.

Monocular transparency is not a new form of unpaired stereopsis

Howard and Duke (2003) generated stereograms with a grey transparent square offset from a vertical bar in one eye, and a vertical bar with a gap in the other eye. They argued that these displays were 'without conventional disparity' and that the metrical depth experienced was a new form of unpaired stereopsis due to 'transparency rather than occlusion'. Another possibility is that the perceived depth in these displays was obtained from horizontal contours. To test this possibility, we generated three displays that contained similar horizontal contourterminations, but were inconsistent with transparency. Reliable depth was seen in all stimuli. We conclude that in our stimuli, and those of Howard and Duke, transparency is not responsible for the perception of depth, which appears to be based instead on disparate horizontal contour terminations. Our results also show that disparate contours of opposite contrast polarity can generate depth.

Defective NF-kappaB Activation in Response to LPS in Type 1 Diabetes Dendritic Cells

Dendritic cells (DC) are the potent antigen presenting cells which modulate T cell responses to self or non-self antigens. DC play a significant role in the pathogenesis of autoimmune diseases, inflammation and infection, but also in the maintenance of tolerance. NF-kappaB, particularly RelB is a crucial pathway for myeloid DC differentiation and functional maturation. While the current paradigm is that mature, nuclear RelB+ DC prime T cells for immunity/autoimmunity and immature DC for tolerance, RelB-deficient mice paradoxically develop generalised systemic autoimmune inflammatory disease with myelopoiesis and splenomegaly. Previous studies suggested abnormal DC differentiation in healthy relatives of type 1 diabetes (t1dm) patients. Therefore, we compared NF- kB activation in monocyte-derived DC from t1dm and non-t1dm controls in response to LPS. While resting DC appeared normal, DC from 6 out of 7 t1dm patients but no t2dm or rheumatoid arthritis patients failed to translocate NF- kB subunits to the nucleus in response to LPS, along with a failure to up-regulate expression of cell surface CD40 and MHC class I. NF- kB subunit mRNA increased normally in t1dm DC after LPS. Both the classical or non-canonical NF- kB pathways were affected as both TNF-a and CD40 stimulation led to a similarly abnormal NF- kB response. In contrast, expression of phosphorylated p38 MAPK and pro-inflammatory cytokine production was intact. These abnormalities in NF- kB activation appear to be generally and specifically applicable at a post-translational level in t1dm, and have the capacity to profoundly influence immunoregulation in affected individuals.

Response programming in dementia of the Alzheimer type: A kinematic analysis

Although planning is important for the functioning of patients with dementia of the Alzheimer Type (DAT), little is known about response programming in DAT. This study used a cueing paradigm coupled with quantitative kinematic analysis to document the preparation and execution of movements made by a group of 12 DAT patients and their age and sex matched controls. Participants connected a series of targets placed upon a WACOM SD420 graphics tablet, in response to the pattern of illumination of a set of light emitting diodes (LEDs). In one condition, participants could programme the upcoming movement, whilst in another they were forced to reprogramme this movement on-line (i.e. they were not provided with advance information about the location of the upcoming target). DAT patients were found to have programming deficits, taking longer to initiate movements; particularly in the absence of cues. While problems spontaneously programming a movement might cause a greater reliance upon on-line guidance, when both groups were required to guide the movement on-line, DAT patients continued to show slower and less efficient movements implying declining sensori-motor function; these differences were not simply due to strategy or medication status. (C) 1997 Elsevier Science Ltd.

An investigation of the anti-pronation effect of two taping methods after application and exercise

This study investigated the effect of two anti-pronation taping techniques on vertical navicular height, an indicator of foot pronation, after its application and 20 min of exercise. The taping techniques were: the low dye (LD) and low dye with the addition of calcaneal slings and reverse sixes (LDCR). A repeated measures study was used. It found that LDCR was superior to LD and control immediately after application and exercise. LD was better than control immediately after application but not after exercise. These findings provide practical directions to clinicians regularly using anti-pronation taping techniques.

Impairments of movement kinematics in patients with Huntington's disease: A comparison with and without a concurrent task

This study aimed to quantify the efficiency and smoothness of voluntary movement in Huntington's disease (HD) by the use of a graphics tablet that permits analysis of movement profiles. In particular, we aimed to ascertain whether a concurrent task (digit span) would affect the kinematics of goal-directed movements. Twelve patients with HD and their matched controls performed 12 vertical zig-zag movements, with both left and right hands (with and without the concurrent task), to large or small circular targets over long or short extents. The concurrent task was associated with shorter movement times and reduced right-hand superiority. Patients with HD were overall slower, especially with long strokes, and had similar peak velocities for both small and large targets, so that controls could better accommodate differences in target size. Patients with HD spent more time decelerating, especially with small targets, whereas controls allocated more nearly equal proportions of time to the acceleration and deceleration phases of movement, especially with large targets. Short strokes were generally less force inefficient than were long strokes, especially so for either hand in either group in the absence of the concurrent task, and for the right hand in its presence. With the concurrent task, however, the left hand's behavior changed differentially for the two groups; for patients with HD, it became more force efficient with short strokes and even less efficient with long strokes, whereas for controls, it became more efficient with long strokes. Controls may be able to divert attention away from the inferior left hand, increasing its automaticity, whereas patients with HD, because of disease, may be forced to engage even further online visual control under the demands of a concurrent task. Patients with HD may perhaps become increasingly reliant on terminal visual guidance, which indicates an impairment in constructing and refining an internal representation of the movement necessary for its. effective execution. Basal ganglia dysfunction may impair the ability to use internally generated cues to guide movement.

Aerobic Exercise Training-Induced Left Ventricular Hypertrophy Involves Regulatory MicroRNAs, Decreased Angiotensin-Converting Enzyme-Angiotensin II, and Synergistic Regulation of Angiotensin-Converting Enzyme 2-Angiotensin (1-7)

Aerobic exercise training leads to a physiological, nonpathological left ventricular hypertrophy; however, the underlying biochemical and molecular mechanisms of physiological left ventricular hypertrophy are unknown. The role of microRNAs regulating the classic and the novel cardiac renin-angiotensin (Ang) system was studied in trained rats assigned to 3 groups: (1) sedentary; (2) swimming trained with protocol 1 (T1, moderate-volume training); and (3) protocol 2 (T2, high-volume training). Cardiac Ang I levels, Ang-converting enzyme (ACE) activity, and protein expression, as well as Ang II levels, were lower in T1 and T2; however, Ang II type 1 receptor mRNA levels (69% in T1 and 99% in T2) and protein expression (240% in T1 and 300% in T2) increased after training. Ang II type 2 receptor mRNA levels (220%) and protein expression (332%) were shown to be increased in T2. In addition, T1 and T2 were shown to increase ACE2 activity and protein expression and Ang (1-7) levels in the heart. Exercise increased microRNA-27a and 27b, targeting ACE and decreasing microRNA-143 targeting ACE2 in the heart. Left ventricular hypertrophy induced by aerobic training involves microRNA regulation and an increase in cardiac Ang II type 1 receptor without the participation of Ang II. Parallel to this, an increase in ACE2, Ang (1-7), and Ang II type 2 receptor in the heart by exercise suggests that this nonclassic cardiac renin-angiotensin system counteracts the classic cardiac renin-angiotensin system. These findings are consistent with a model in which exercise may induce left ventricular hypertrophy, at least in part, altering the expression of specific microRNAs targeting renin-angiotensin system genes. Together these effects might provide the additional aerobic capacity required by the exercised heart. (Hypertension. 2011;58:182-189.).

Congenic strains provide evidence that four mapped loci in chromosomes 2, 4, and 16 influence hypertension in the SHR

Aneas I, Rodrigues MV, Pauletti BA, Silva GJ, Carmona R, Cardoso L, Kwitek AE, Jacob HJ, Soler JM, Krieger JE. Congenic strains provide evidence that four mapped loci in chromosomes 2, 4, and 16 influence hypertension in the SHR. Physiol Genomics 37: 52-57, 2009. First published January 6, 2009; doi: 10.1152/physiolgenomics.90299.2008. - To dissect the genetic architecture controlling blood pressure (BP) regulation in the spontaneously hypertensive rat (SHR) we derived congenic rat strains for four previously mapped BP quantitative trait loci (QTLs) in chromosomes 2, 4, and 16. Target chromosomal regions from the Brown Norway rat (BN) averaging 13 - 29 cM were introgressed by marker-assisted breeding onto the SHR genome in 12 or 13 generations. Under normal salt intake, QTLs on chromosomes 2a, 2c, and 4 were associated with significant changes in systolic BP (13, 20, and 15 mmHg, respectively), whereas the QTL on chromosome 16 had no measurable effect. On high salt intake (1% NaCl in drinking water for 2 wk), the chromosome 16 QTL had a marked impact on SBP, as did the QTLs on chromosome 2a and 2c (18, 17, and 19 mmHg, respectively), but not the QTL on chromosome 4. Thus these four QTLs affected BP phenotypes differently: 1) in the presence of high salt intake (chromosome 16), 2) only associated with normal salt intake (chromosome 4), and 3) regardless of salt intake (chromosome 2c and 2a). Moreover, salt sensitivity was abrogated in congenics SHR. BN2a and SHR. BN16. Finally, we provide evidence for the influence of genetic background on the expression of the mapped QTLs individually or as a group. Collectively, these data reveal previously unsuspected nuances of the physiological roles of each of the four mapped BP QTLs in the SHR under basal and/or salt loading conditions unforeseen by the analysis of the F2 cross.

Neural activity changes to emotional stimuli in healthy individuals under chronic use of clomipramine

Previous functional magnetic resonance imaging (fMRI) studies examined neural activity responses to emotive stimuli in healthy individuals after acute/subacute administration of antidepressants. We now report the effects of repeated use of the antidepressant clomipramine on fMRI data acquired during presentation of emotion-provoking and neutral stimuli on healthy volunteers. A total of 12 volunteers were evaluated with fMRI after receiving low doses of clomipramine for 4 weeks and again after 4 weeks of washout. Fear-, happiness-, anger-provoking and neutral pictures from the International Affective Picture System (IAPS) were used. Data analysis was performed with statistical parametric mapping (P < 0.05). Paired t-test comparisons for each condition between medicated and unmedicated states showed, to negative valence paradigms, decrease in brain activity in the amygdala when participants were medicated. We also demonstrated, across both positive and negative valence paradigms, consistent decreases in brain activity in the medicated state in the anterior cingulate gyrus and insula. This is the first report of modulatory effects of repeated antidepressant use on the central representation of somatic states in response to emotions of both negative and positive valences in healthy individuals. Also, our results corroborate findings of antidepressant-induced temporolimbic activity changes to emotion-provoking stimuli obtained in studies of subjects treated acutely with such agents.

Functional asymmetries in the movement kinematics of patients with Tourette's syndrome

Objectives-This study adopted a concurrent task design and aimed to quantify the efficiency and smoothness of voluntary movement in Tourette's syndrome via the use of a graphics tablet which permits analysis of movement profiles. In particular, the aim was to ascertain whether a concurrent task (digit span) would affect the kinematics of goal directed movements, and whether patients with Tourette's syndrome would exhibit abnormal functional asymmetries compared with their matched controls. Methods-Twelve patients with Tourette's syndrome and their matched controls performed 12 vertical zig zag movements, with both left and right hands (with and without the concurrent task), to large or small targets over long or short extents. Results-With short strokes, controls showed the predicted right hand superiority in movement time more strongly than patients with Tourette's syndrome, who instead showed greater hand symmetry with short strokes. The right hand of controls was less force efficient with long strokes and more force efficient with short strokes, whereas either hand of patients with Tourette's syndrome was equally force efficient, irrespective of stroke length, with an overall performance profile similar to but better than that of the controls' left hand. The concurrent task, however, increased the force efficiency of the right hand in patients with Tourette's syndrome and the left hand in controls. Conclusions-Patients with Tourette's syndrome, compared with controls, were not impaired in the performance of fast, goal directed movements such as aiming at targets; they performed in certain respects better than controls. The findings clearly add to the growing literature on anomalous lateralisation in Tourette's syndrome, which may be explained by the recently reported loss of normal basal ganglia asymmetries in that disorder.

Predicting relationships between speed and accuracy of targetting movements is important

While explaining a large proportion of any variance, accounts of the speed and accuracy of targetting movements use techniques (e.g., log transforms) that typically reduce variability before ''explaining'' the data. Therefore the predictive power of such accounts are important. We consider whether Plamondon's model can account for kinematics of targetting movements of clinical populations.

From lateral to mesial: The quest for a surgical cure for temporal lobe epilepsy

Purpose: A gap of more than a hundred years occurred between the first accounts of mesial temporal sclerosis and recognition of its role in the pathogenesis of psychomotor seizures. This paper reviews how the understanding and surgical treatment of temporal lobe epilepsy developed, particularly from the work of Penfield, Jasper, and their associates at the Montreal Neurological Institute (MNI). Methods: Publications on EEG and surgery for temporal lobe seizures from 1935 to 1953 were reviewed and charts of selected patients operated on at the MNI in the same period were examined. Attention was focused on the evolution of surgical techniques for temporal lobe epilepsy. Results: In the late 1930s, some EEG findings suggested deep-lying disturbances originating in the temporal lobe. However, it took another two decades before the correlation of clinical, neurophysiological, and anatomical findings provided evidence for the involvement of the mesial structures in psychomotor or temporal lobe seizures. From 1949 and onward, Penfield and his associates applied this evidence to extend the surgical resections to include the uncus and the hippocampus. Conclusion: The collaborative work of a team led by Penfield and Jasper at the MNI helped to define the role of neurophysiological studies in epilepsy surgery. As a result, the importance of removing the mesial structures in order to obtain better seizure control in patients with temporal lobe epilepsy became firmly established.