Altered Auditory BOLD Response to Conspecific Birdsong in Zebra Finches with Stuttered Syllables

How well a songbird learns a song appears to depend on the formation of a robust auditory template of its tutor's song. Using functional magnetic resonance neuroimaging we examine auditory responses in two groups of zebra finches that differ in the type of song they sing after being tutored by birds producing stuttering-like syllable repetitions in their songs. We find that birds that learn to produce the stuttered syntax show attenuated blood oxygenation level-dependent (BOLD) responses to tutor's song, and more pronounced responses to conspecific song primarily in the auditory area field L of the avian forebrain, when compared to birds that produce normal song. These findings are consistent with the presence of a sensory song template critical for song learning in auditory areas of the zebra finch forebrain. In addition, they suggest a relationship between an altered response related to familiarity and/or saliency of song stimuli and the production of variant songs with stuttered syllables

Sexual dimorphism in striatal dopaminergic responses promotes monogamy in social songbirds

In many songbird species, males sing to attract females and repel rivals. How can gregarious, non-territorial songbirds such as zebra finches, where females have access to numerous males, sustain monogamy? We found that the dopaminergic reward circuitry of zebra finches can simultaneously promote social cohesion and breeding boundaries. Surprisingly, in unmated males but not in females, striatal dopamine neurotransmission was elevated after hearing songs. Behaviorally too, unmated males but not females persistently exchanged mild punishments in return for songs. Song reinforcement diminished when dopamine receptors were blocked. In females, we observed song reinforcement exclusively to the mate’s song, although their striatal dopamine neurotransmission was only slightly elevated. These findings suggest that song-triggered dopaminergic activation serves a dual function in social songbirds: as low-threshold social reinforcement in males and as ultra-selective sexual reinforcement in females. Co-evolution of sexually dimorphic reinforcement systems can explain the coexistence of gregariousness and monogamy

Functional Brain Network Changes Associated with Maintenance of Cognitive Function in Multiple Sclerosis

In multiple sclerosis (MS) functional changes in connectivity due to cortical reorganization could lead to cognitive impairment (CI), or reflect a re-adjustment to reduce the clinical effects of widespread tissue damage. Such alterations in connectivity could result in changes in neural activation as assayed by executive function tasks. We examined cognitive function in MS patients with mild to moderate CI and age-matched controls. We evaluated brain activity using functional magnetic resonance imaging (fMRI) during the successful performance of the Wisconsin card sorting (WCS) task by MS patients, showing compensatory maintenance of normal function, as measured by response latency and error rate. To assess changes in functional connectivity throughout the brain, we performed a global functional brain network analysis by computing voxel-by-voxel correlations on the fMRI time series data and carrying out a hierarchical cluster analysis. We found that during the WCS task there is a significant reduction in the number of smaller size brain functional networks, and a change in the brain areas representing the nodes of these networks in MS patients compared to age-matched controls. There is also a concomitant increase in the strength of functional connections between brain loci separated at intermediate-scale distances in these patients. These functional alterations might reflect compensatory neuroplastic reorganization underlying maintenance of relatively normal cognitive function in the face of white matter lesions and cortical atrophy produced by MS

Pairwise comparisons of BOLD responses.

<p>Scatterplots of magnitude of BOLD response in the medial posterior forebrain, comparing the four different stimuli, namely TONE, conspecific song (CON), bird's own song (BOS) and tutor's song (TUT), pairwise in medial parasagittal slices, in 8 repeaters (red dots) and non-repeaters (black dots) each. Note that most of the red dots fall below the diagonal when TUT is compared with CON and BOS. p-values at the top of each panel indicate significance for the hypothesis that the two stimuli of that panel elicited the same response (Wilcoxon signed rank test), for non-repeaters and repeaters each.</p

Correlation of BOLD response with tutor's song similarity.

<p>The volume of response to TUT in non-repeaters and repeaters, expressed as a percentage of the mean of all stimuli in each bird, is plotted as a function of the % similarity of the pupil's song with that of its tutor. The % similarity values obtained with the asymmetric time course motif comparison method (A) using the Sound Analysis Pro program <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0014415#pone.0014415-Tchernichovski1" target="_blank">[25]</a>, <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0014415#pone.0014415-Deregnaucourt1" target="_blank">[26]</a> show no statistically significant correlation in repeaters (red dots) or non-repeaters (black dots); however, values obtained using the symmetric method (B) shows positive linear correlation in repeaters, but not in non-repeaters. Linear fit to the data is indicated by the blue and green lines.</p

Song learning in syllable repeaters and non-repeaters.

<p><b>A.</b> Spectrograms of non-repeater (left) and repeater (right) song motifs. The R's indicate repeated syllables. <b>B.</b> Learning of tutor's songs by tutored repeaters and non-repeaters. Bar graphs show no significant difference in % similarity, mean accuracy and sequential match of pupil song motifs with the respective tutor motifs, between repeaters (n = 8) and non-repeaters (n = 8) tutored by repeater tutors in this study. The error bars represent standard errors of the mean (SEMs) <b>C.</b> Spectrograms of the songs of a tutor and its two pupils as adults, one of which is a repeater and the other a non-repeater. Repeated syllables in the tutor's as well as repeater pupil's song are indicated by the letter “R”.</p

Functional MRI in syllable repeaters and non-repeaters.

<p><b>A.</b> BOLD activations averaged over 8 non-repeater birds (“non-repeaters”) and 8 birds with syllable repetitions (“repeaters”) for the four auditory stimuli, tutor's song (TUT), 2 kHz pure tone (TONE), bird's own song (BOS) and conspecific song (CON). The type of stimulus is indicated on the left of each panel. The distance of the slice midlines from the midline of the brain is shown at the bottom. For the next-to-midline slice, the outline of the cerebrum is indicated, and in the first set of images the region of interest is shown as the area between the dotted lines and the border of the cerebrum. In the images labeled “Non-repeaters” and “Repeaters”, colors denote correlation coefficients R, which are overlaid on corresponding anatomical brain MRI sections. In the images labeled “Difference” color corresponds to the difference in z-values (non-repeaters – repeaters). The red end of the color scale corresponds to R = 0.097 or ΔZ = −8.8 (each corresponding to p<10⁻⁶, multiple test corrected). The yellow end of the R color scale is scaled individually. Activations from the right and left hemispheres of the brain are averaged. The main activated area that is consistently activated in all images corresponds to L/CM/NCM region. Even though CON activates the auditory areas in all non-repeater birds, unlike repeaters, no activated voxels are seen in the averaged images of non-repeaters. This is most likely because there is less consistency in non-repeaters compared to repeaters in the precise location of activated voxels. In accordance with this, the difference image does not show significant differences. <b>B.</b> Comparison of the volume and magnitude of BOLD response in the medial posterior area containing field L and small portions of CM and NCM for TUT, TONE, BOS and CON stimuli in repeaters and non-repeaters. Comparisons of normalized data between non-repeater and repeater birds for each stimulus, corresponding to the shown bar plots, using Student's t test show statistically significant difference for TUT with respect to both % magnitude (p = 0.003, df = 7) and % volume (p = 0.05, df = 7). For CON the difference is significant with respect to % magnitude (p = 0.048, df = 7), but not with respect to % volume. The corresponding values for TONE (% magnitude – p = 0.27, df = 7; % volume – p = 0.56, df = 7) and BOS (% magnitude – p = 0.64, df = 7; % volume – p = 0.48, df = 7) are not significant at the 5% error probability level. The error bars in the figure represent SEMs. A two-way ANOVA on the (non-normalized) BOLD response magnitude data over both groups and stimuli gives for the stimuli p = 0.02 (F = 3.52), for the groups p = 0.24 (F = 1.41), and for the interaction p = 0.01 (F = 3.84). The corresponding values on the BOLD activation volume are p = 0.20 (F = 1.61), p = 0.37 (F = 0.82), and p = 0.47 (F = 0.85), respectively. Two-way ANOVA only makes sense if the data are not normalized because the within-bird normalization erases differences with respect to groups. These results are overall consistent with the non-parametric analysis on the non-normalized data shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0014415#pone-0014415-g003" target="_blank">Figure 3</a>.</p

Evaluating noninvasive brain stimulation to treat overactive bladder in individuals with multiple sclerosis: a randomized controlled trial protocol

Abstract Background Multiple Sclerosis (MS) is an often debilitating disease affecting the myelin sheath that encompasses neurons. It can be accompanied by a myriad of pathologies and adverse effects such as neurogenic lower urinary tract dysfunction (NLUTD). Current treatment modalities for resolving NLUTD focus mainly on alleviating symptoms while the source of the discomfort emanates from a disruption in brain to bladder neural circuitry. Here, we leverage functional magnetic resonance imaging (fMRI), repetitive transcranial magnetic stimulation (rTMS) protocols and the brains innate neural plasticity to aid in resolving overactive bladder (OAB) symptoms associated with NLUTD. Methods By employing an advanced neuro-navigation technique along with processed fMRI and diffusion tensor imaging data to help locate specific targets in each participant brain, we are able to deliver tailored neuromodulation protocols and affect either an excitatory (20 min @ 10 Hz, applied to the lateral and medial pre-frontal cortex) or inhibitory (20 min @ 1 Hz, applied to the pelvic supplemental motor area) signal on neural circuitry fundamental to the micturition cycle in humans to restore or reroute autonomic and sensorimotor activity between the brain and bladder. Through a regimen of questionnaires, bladder diaries, stimulation sessions and analysis, we aim to gauge rTMS effectiveness in women with clinically stable MS. Discussion Some limitations do exist with this study. In targeting the MS population, the stochastic nature of MS in general highlights difficulties in recruiting enough participants with similar symptomology to make meaningful comparisons. As well, for this neuromodulatory approach to achieve some rate of success, there must be enough intact white matter in specific brain regions to receive effective stimulation. While we understand that our results will represent only a subset of the MS community, we are confident that we will accomplish our goal of increasing the quality of life for those burdened with MS and NLUTD. Trial registration This trial is registered at ClinicalTrials.gov (NCT06072703), posted on Oct 10, 2023