Object working memory performance depends on microstructure of the frontal-occipital fasciculus

Abstract

Re-entrant circuits involving communication between the frontal cortex and other brain areas have been hypothesized to be necessary for maintaining the sustained patterns of neural activity that represent information in working memory, but evidence has so far been indirect. If working memory maintenance indeed depends on such temporally precise and robust long-distance communication, then performance on a delayed recognition task should be highly dependent on the microstructural integrity of white-matter tracts connecting sensory areas with prefrontal cortex. This study explored the effect of variations in white-matter microstructure on working memory performance in two separate groups of participants: patients with multiple sclerosis and age- and sex-matched healthy adults. Functional magnetic resonance imaging was performed to reveal cortical regions involved in spatial and object working memory, which, in turn, were used to define specific frontal to extrastriate white-matter tracts of interest via diffusion tensor tractography. After factoring out variance due to age and the microstructure of a control tract (the corticospinal tract), the number of errors produced in the object working memory task was specifically related to the microstructure of the inferior frontal-occipital fasciculus. This result held for both groups, independently, providing a within-study replication with two different types of white-matter structural variability: multiple sclerosis-related damage and normal variation. The results demonstrate the importance of interactions between specific regions of the prefrontal cortex and sensory cortices for a nonspatial working memory task that preferentially activates those regions.

FIG. 1.

Delayed-recognition task. Participants were given one of three instruction screens: identity, location, or nothing. In the identity condition, participants were to remember the identity of the faces presented independent of the locations. When the test stimulus appeared after the memory delay, participants pressed one of two buttons to indicate whether the test face was the same as any of the three sample faces. In the location condition, participants were to remember, and respond according to, the location of the faces independent of the identity of the faces. In the nothing condition participants did not need to remember anything and needed only to respond at the test screen by pressing both buttons.

FIG. 2.

Functional magnetic resonance imaging activations comparing all working memory activity greater than delay activity. This contrast yielded a group of frontal and posterior regions of interest. The frontal regions of interest included the anterior middle frontal gyrus (blue), the junction of the inferior frontal sulcus with the precentral sulcus (green), and superior frontal sulcus (red). The posterior regions of interest included the fusiform gyrus (green), the intraparietal sulcus/superior parietal lobule region (red), and the temporal-occipital junction, which is roughly dorsal and posterior to the fusiform gyrus region shown here. The colors correspond to the relevant fiber tracts in Figure 3.

FIG. 3.

An individual's fiber tracking results exhibiting the three white-matter tracts of interest. The red curve corresponds to a dorsal portion of the superior longitudinal fasciculus. The green tract corresponds to a ventral portion of the superior longitudinal fasciculus. The blue tract corresponds to a portion of the inferior frontal occipital fasciculus.

FIG. 4.

An example of the fronto-occipital fasciculus fractional anisotropy profile. Location along the tract is indicated in millimeters (mm) relative to the anterior commissure (AC). The normal average curve is plotted as the black bold line. The dashed lines represent±0.5 standard deviation from the mean. An individual with multiple sclerosis (MS) with a good curve fit is plotted in blue; the model fit is R²=0.967 (residual R²=0.029). An individual with MS with a bad curve fit is plotted in red; the model fit is R²=0.198 (residual R²=0.802).

FIG. 5.

White-matter tract curve fit residuals for all individual participants. Note that individuals with multiple sclerosis exhibited greater variability in fractional anisotropy curve fit residual values. dSLF, dorsal portion of the superior longitudinal fasciculus; IFO, fronto-occipital fasciculus; vSLF, ventral portion of the superior longitudinal fasciculus.

FIG 6.

Correlations between object accuracy and fronto-occipital fasciculus (IFO) integrity. Note that although IFO variability in the control group (right) is not as high as that in the multiple sclerosis (MS) group (left), a very strong correlation between IFO integrity and performance on the object working memory task is seen in both groups.