Mean percentage of conditioned responses (CR incidence) in paired (e.g., acquisition) trials.

<p>CR incidence and standard errors (SE) are shown per block of ten trials (Total = Mean total percentage CR incidence) in DMD patients (white dots and column) and in control subjects (black dots and column).</p

Cerebellar-Dependent Associative Learning Is Preserved in Duchenne Muscular Dystrophy: A Study Using Delay Eyeblink Conditioning

<div><p>Objective</p><p>Besides progressive muscle weakness cognitive deficits have been reported in patients with Duchenne muscular dystrophy (DMD). Cerebellar dysfunction has been proposed to explain cognitive deficits at least in part. In animal models of DMD disturbed Purkinje cell function has been shown following loss of dystrophin. Furthermore there is increasing evidence that the lateral cerebellum contributes to cognitive processing. In the present study cerebellar-dependent delay eyeblink conditioning, a form of associative learning, was used to assess cerebellar function in DMD children.</p><p>Methods</p><p>Delay eyeblink conditioning was examined in eight genetically defined male patients with DMD and in ten age-matched control subjects. Acquisition, timing and extinction of conditioned eyeblink responses (CR) were assessed during a single conditioning session.</p><p>Results</p><p>Both groups showed a significant increase of CRs during the course of learning (block effect p < 0.001). CR acquisition was not impaired in DMD patients (mean total CR incidence 37.4 ± 17.6%) as compared to control subjects (36.2 ± 17.3%; group effect p = 0.89; group by block effect p = 0.38; ANOVA with repeated measures). In addition, CR timing and extinction was not different from controls.</p><p>Conclusions</p><p>Delay eyeblink conditioning was preserved in the present DMD patients. Because eyeblink conditioning depends on the integrity of the intermediate cerebellum, this older part of the cerebellum may be relatively preserved in DMD. The present findings agree with animal model data showing that the newer, lateral cerebellum is primarily affected in DMD.</p></div

Eyeblink conditioning in an individual DMD patient and control subject.

<p>Rectified and filtered EMG data of the orbicularis oculi muscle of 100 paired CS-US trials are shown from the beginning of the experiment (top) to the end (bottom). The first vertical line indicates the CS onset and the second the beginning of the US. Responses occurring within the 150 ms interval after CS onset (dotted line) were considered alpha-responses and were not counted as CRs. See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0126528#sec006" target="_blank">Methods</a> for further details.</p

Eyeblink conditioning in an individual DMD patient and control subject.

<p>Rectified and filtered EMG data of the orbicularis oculi muscle of 100 paired CS-US trials are shown from the beginning of the experiment (top) to the end (bottom). The first vertical line indicates the CS onset and the second the beginning of the US. Responses occurring within the 150 ms interval after CS onset (dotted line) were considered alpha-responses and were not counted as CRs. See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0126528#sec006" target="_blank">Methods</a> for further details.</p

Timing of conditioned and unconditioned eyeblink responses.

<p>Mean values and standard deviations (SD) of onset (black columns) and peaktime latencies (white columns) of conditioned eyeblink responses in paired trials and unconditioned eyeblink responses in unpaired trials in DMD patients and control subjects. Values for onset and peaktime refer to the time as related to the onset of the US (air puff), set as 0 ms.</p

Clinical characteristics and X-chromosomal genetic findings in DMD patients.

<p>Examination of limb coordination, balance and gait and the use of ataxia scales to determine the severity of cerebellar signs was not meaningful in case of muscle weakness. Muscle strength was examined according to the graduation of the Medical Research Council (MRC). Abbr.: + = mild, ++ = moderate; A. = Ankle; Dis. = Disorder; n.a. = not applicable in case of muscle weakness. See <i><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0126528#sec006" target="_blank">Methods</a></i>for further details.</p><p>Clinical characteristics and X-chromosomal genetic findings in DMD patients.</p

The relation between motor function and leptin SDS in terms of SMA type, showing that the lower the overall motor function, the higher was the risk for elevated leptin levels.

<p>Vertical lines in bold at -2 SD and +2 SD indicate the reference range for leptin SDS. <b>As a consequence, lower motor function is linked to high leptin-SDS independent of SMA type</b>.</p

Distribution of auxological data in SMA patients (BMI = body mass index, WC = waist circumference, HC = hip circumference, WHR waist-to-hip ratio, SDS = standard deviation score).

<p>Vertical lines in bold (- 2 SD, + 2 SD) indicate the reference range. Boxes indicate the interquartile range (IQR), whiskers indicate 1.5xIQR, black dots are outliers. Asterisks indicate a significant deviation of the median from zero (p <0.01) with a shift towards higher values for WHR and leptin, as well as a shift to lower values for weight, height, BMI und HC.</p

Association between leptin SDS and motor function.

<p>Association between leptin SDS and motor function.</p

Association between leptin SDS and SMA type.

<p>Association between leptin SDS and SMA type.</p