Discussion

Generative and recognition models for neuroanatomy☆

Individuals with persistent developmental stuttering display deficits in aligning motor actions to external cues (i.e., sensorimotor synchronization). Diffusion imaging studies point to stuttering-associated differences in dorsal, not ventral, white matter pathways, and in the cerebellar peduncles. Here, we studied microstructural white matter differences between adults who stutter (AWS) and fluent speakers using two complementary approaches to: (a) assess previously reported group differences in white matter diffusivity, and (b) evaluate the relationship between white matter diffusivity and sensorimotor synchronization in each group.

Participants completed a sensorimotor synchronization task and a diffusion MRI scan. We identified the cerebellar peduncles and major dorsal- and ventral-stream language pathways in each individual and assessed correlations between sensorimotor synchronization and diffusion measures along the tracts.

The results demonstrated group differences in dorsal, not ventral, language tracts, in alignment with prior reports. Specifically, AWS had significantly lower fractional anisotropy (FA) in the left arcuate fasciculus, and significantly higher mean diffusivity (MD) in the bilateral frontal aslant tract compared to fluent speakers, while no significant group difference was detected in the inferior fronto-occipital fasciculus. We also found significant group differences in both FA and MD of the left middle cerebellar peduncle. Comparing patterns of association with sensorimotor synchronization revealed a novel double dissociation: MD within the left inferior cerebellar peduncle was significantly correlated with mean asynchrony in AWS but not in fluent speakers, while FA within the left arcuate fasciculus was significantly correlated with mean asynchrony in fluent speakers, but not in AWS.

Our results support the view that stuttering involves altered connectivity in dorsal tracts and that AWS may rely more heavily on cerebellar tracts to process timing information. Evaluating microstructural associations with sensitive behavioral measures provides a powerful tool for discovering additional functional differences in the underlying connectivity in AWS.

The ability to recognize the structural components of words, known as morphological processing, was recently associated with the bilateral ventral white matter pathways, across different writing systems. However, it remains unclear whether these associations are specific to the context of reading. To shed light on this question, in the current study we investigated whether the ventral pathways are associated with morphological processing in an oral word production task that does not involve reading. Forty-five participants completed a morpheme-based fluency task in Hebrew, as well as diffusion MRI (dMRI) scans. We used probabilistic tractography to segment the major ventral and dorsal white matter pathways, and assessed the correlations between their microstructural properties and performance on the morpheme-based fluency task. We found significant correlations between morpheme-based fluency and properties of the bilateral ventral tracts, suggesting that the involvement of these tracts in morphological processing extends beyond the reading modality. In addition, significant correlations were found in the frontal aslant tract (FAT), a dorsal tract associated with oral fluency and speech production. Together, our findings emphasize that neurocognitive associations reflect both the cognitive construct under investigation as well as the task used for its assessment. Lastly, to elucidate the biological factors underlying these correlations, we incorporated the composite hindered and restricted model of diffusion (CHARMED) framework, measured in independent scans. We found that only some of our findings could be attributed to variation in a CHARMED-based estimate of fiber density. Further, we were able to uncover additional correlations that could not be detected using traditional dMRI indices. In sum, our results show that the involvement of the ventral tracts in morphological processing extends to the production domain, and demonstrate the added value of including sensitive structural measurements in neurocognitive investigations.

The spatial coordinate system in which a stimulus representation is embedded is known as its reference frame. Every visual representation has a reference frame [1], and the visual system uses a variety of reference frames to efficiently code visual information [e.g., 1, 2, 3, 4, 5]. The representation of faces in early stages of visual processing depends on retino-centered reference frames, but little is known about the reference frames that code the high-level representations used to make judgements about faces. Here, we focus on a rare and striking disorder of face perception—hemi-prosopometamorphopsia (hemi-PMO)—to investigate these reference frames. After a left splenium lesion, Patient A.D. perceives features on the right side of faces as if they had melted. The same features were distorted when faces were presented in either visual field, at different in-depth rotations, and at different picture-plane orientations including upside-down. A.D.’s results indicate faces are aligned to a view- and orientation-independent face template encoded in a face-centered reference frame, that these face-centered representations are present in both the left and right hemisphere, and that the representations of the left and right halves of a face are dissociable.

Skilled readers differ in their sensitivity to morphological word structure, which captures useful regularities in the mapping between written word forms and their meaning. We recently showed that sensitivity to morphological information in adult English readers is associated with the ventral reading pathways, bilaterally. It remains unclear, however, whether this association is specific to the English writing system. To shed light on this question, we investigated whether the associations between the ventral reading pathways and morphological sensitivity to word structure generalize across languages with different orthographies and morphological systems. To this end, we assessed neurocognitive correlations between white matter structural properties and morphological sensitivity in Hebrew, a Semitic language where morphemes are combined in a non-linear manner. We used diffusion MRI (dMRI) to segment ventral and dorsal tracts of interest in a sample of 43 adult Hebrew readers, who also completed a behavioral language assessment battery that included a morphological task. Significant correlations were found between morphological sensitivity and properties of bilateral ventral, but not dorsal, tracts. These correlations remained significant after controlling for measures of vocabulary and word reading, demonstrating their specificity to the morphological task. The current findings in Hebrew show striking similarity to prior findings in English. Our results support the view that morphological information contributes to lexical access along the ventral pathways, across orthographies and morphological systems.

Adolescence is characterized by rapid brain development in white matter (WM) that is attributed in part to surges in gonadal hormones. To date, however, there have been few longitudinal investigations relating changes in gonadal hormones and WM development in adolescents. We acquired diffusion-weighted MRI to estimate mean fractional anisotropy (FA) from 10 WM tracts and salivary testosterone from 51 females and 29 males (ages 9–14 years) who were matched on pubertal stage and followed, on average, for 2 years. We tested whether interactions between sex and changes in testosterone levels significantly explained changes in FA. We found positive associations between changes in testosterone and changes in FA within the corpus callosum, cingulum cingulate, and corticospinal tract in females (all ps<0.05, corrected) and non-significant associations in males. We also collected salivary estradiol from females and found that increases in estradiol were associated with increases in FA in the left uncinate fasciculus (p = 0.04, uncorrected); however, this effect was no longer significant after accounting for changes in testosterone. Our findings indicate there are sex differences in how changes in testosterone relate to changes in WM microstructure of tracts that support impulse control and emotion regulation across the pubertal transition.

Morphological processing, the ability to extract information about word structure, is an essential component of reading. Functional MRI studies have identified several cortical regions involved in morphological processing, but the white matter pathways that support this skill remain unknown. Here, we examine the relationship between behavioral measures of morphological processing and microstructural properties of white matter pathways. Using diffusion MRI (dMRI), we identified the major ventral and dorsal reading pathways in a group of 45 adult English readers. The same participants completed a behavioral battery that included a morphological task and measures of phonological and orthographic processing. We found significant correlations between morphological processing skill and microstructural properties of the ventral, but not dorsal, pathways. These correlations were detected primarily in the left hemisphere, and remained significant after controlling for phonological or orthographic measures, suggesting some level of cognitive specificity. Morphological processing of written words thus appears to rely on ventral pathways, primarily in the left hemisphere. This finding supports the contribution of morphological processing to lexical access and comprehension of complex English words.