García, Xavier (ed.) (2015). Joan Oliver-Joaquim Molas: Diàleg epistolar il·lustrat (1959-1982). Lleida: Pagès Editors, pp. 186

<p><i>Objectives</i>: Attention-deficit/hyperactivity disorder (ADHD) has been associated with spatial working memory as well as frontostriatal core deficits. However, it is still unclear how the link between these frontostriatal deficits and working memory function in ADHD differs in children and adults. This study examined spatial working memory in adults and children with ADHD, focussing on identifying regions demonstrating age-invariant or age-dependent abnormalities. <i>Methods</i>: We used functional magnetic resonance imaging to examine a group of 26 children and 35 adults to study load manipulated spatial working memory in patients and controls. <i>Results</i>: In comparison to healthy controls, patients demonstrated reduced positive parietal and frontostriatal load effects, i.e., less increase in brain activity from low to high load, despite similar task performance. In addition, younger patients showed negative load effects, i.e., a decrease in brain activity from low to high load, in medial prefrontal regions. Load effect differences between ADHD and controls that differed between age groups were found predominantly in prefrontal regions. Age-invariant load effect differences occurred predominantly in frontostriatal regions. <i>Conclusions</i>: The age-dependent deviations support the role of prefrontal maturation and compensation in ADHD, while the age-invariant alterations observed in frontostriatal regions provide further evidence that these regions reflect a core pathophysiology in ADHD.</p

Mean theta EEG GSP and GFS along with GSP/GFS-response accuracy interactions.

<p>Results for GSP (maintenance and baseline interval) are shown in the left panels of <b>A</b>, <b>B</b>, and <b>C</b>, whereas results for the GFS are shown in the right panels of <b>A</b>, <b>B</b>, and <b>C</b>. (** indicates p<0.001, * indicates p<0.05. n.s.: non-significant.</p

Topographical distribution of EEG working memory effects.

<p>For adults and children, load dependent and load independent theta EEG effects are shown in subfigures <b>A</b> and <b>B</b>, respectively. Group differences are shown in <b>C</b> and <b>D</b>. The short arrow indicates p<0.05 (t >1.69) and the long arrow indicates p<0.01 (t >2.44).</p

Theta GSP-BOLD and GFS-BOLD signal correlations.

<p>Within-group results for theta GSP-BOLD signal correlations are shown in <b>A</b>-<b>C</b>, while GFS-BOLD signal correlations are shown in <b>D</b>-<b>F</b>. Between-group comparisons are presented in <b>C</b> and <b>F</b>. For all subfigures, results are shown at p<0.001 (uncorrected), except for subfigure E (p<0.01, uncorrected). Abbreviations: PPC, posterior parietal lobe; MFG, middle frontal gyrus; MPFC, medial prefrontal cortex; PCC, posterior cingulate cortex, R, right hemisphere; L, left hemisphere.</p

Load dependent fMRI activation differences between adults and children.

<p>Results are reported at a voxel threshold of p<0.001 (uncorrected) with a cluster-correction of p<0.05. R, right; L, left; IPL, inferior parietal lobe; STG, superior temporal gyrus; MFG, middle frontal gyrus; SFG, superior frontal gyrus; FG, fusiform gyrus; MPFC, medial prefrontal cortex.</p

Schematic timeline of the experimental design.

<p>ASL: arterial spin labelling, WM: working memory.</p

Representative MEGA-PRESS spectra.

<p>(A) Averaged MEGA-PRESS spectra (averaged across the subject group) acquired at rest (left) and during the WM task. The GABA peak at 3.0 ppm appears to increase between the resting spectrum and the first WM spectrum, and then decrease during performance of the WM task (panels 2-5). The dashed line marks the resting state peak. Glx: glutamate + glutamine concentration, GABA: gamma-aminobutyric acid, NAA: N-acetylaspartate, IU: institutional units. (B) LCModel output for a single subject: the fit is shown in red, superimposed on the edited spectrum (in black). The top panel shows the residuals between the MRS data and the spectral fit.</p

Areas of significant perfusion change during the WM task (p<0.001, uncorrected, k = 150).

<p>The location of the left DLPFC voxel (white rectangle) is shown for comparison. Results are presented on an axial slice (MNI z-coordinate = 24) of a T1-weighted image from a single subject.</p

Resting perfusion map acquired from a single participant, shown in radiological orientation (scale: 0–90 ml/min/100ml).

<p>Resting perfusion map acquired from a single participant, shown in radiological orientation (scale: 0–90 ml/min/100ml).</p

Women show higher perfusion than men and DHEAS correlates negatively with perfusion.

<p>a) Sex difference in whole brain grey matter perfusion: perfusion is higher in women (<i>M</i> = 35.97 ml/min/100 ml, <i>SD</i> = 5.37) than in men (<i>M</i> = 30.47 ml/min/100 ml, <i>SD</i> = 5.91, <i>p</i> = .006). Single dots represent the subjects' individual values. The horizontal line within the boxes indicate medians, the edges of the boxes are the 25^th and 75^th percentiles, and the whiskers represent 1.5 times the interquartile range. b) Sex difference (women > men) in regional perfusion: women show higher regional perfusion than men (<i>p</i> = .004, FWE-corrected). c) Simple regression analysis with whole brain perfusion values as the dependent variable and DHEAS as the only predictor: a significant model was found (<i>p</i> = .007, adjusted <i>R</i>^<i>2</i> = .180) with a standardised β = -.452 for DHEAS. d) DHEAS effects in men and women: DHEAS correlates negatively with regional perfusion in both sexes (<i>p</i> = .004, FWE-corrected). Colour bar in a) and c) denotes a non-parametric <i>t</i> score, given by <i>a1</i>/[standard error(<i>a1</i>)], see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0135827#sec002" target="_blank">methods</a>. Images are shown in neurological orientation. Slices are at MNI z-coordinates -45, -30, -15, 0, 15, 30, 45, 60, 75 (from top left to bottom right).</p