Berman, M. G. | Search bioRxiv

bioRxiv2018

Brain Connectivity Tracks Effects of Chemotherapy Separately from Behavioral Measures

Several studies in cancer research have suggested that cognitive dysfunction following chemotherapy, referred to in lay terms as \"chemobrain\", is a serious problem. At present, the changes in integrative brain function that underlie such dysfunction remains poorly understood. Recent developments in neuroimaging suggest that patterns of functional connectivity can provide a broadly applicable neuromarker of cognitive performance and other psychometric measures. The current study used multivariate analysis methods to identify patterns of disruption in resting state functional connectivity of the brain due to chemotherapy and the degree to which the disruptions can be linked to behavioral measures of distress and cognitive performance. Sixty two women (22 healthy control, 18 patients treated with adjuvant chemotherapy, and 22 treated without chemotherapy) were evaluated with neurocognitive measures followed by self-report questionnaires and open eyes resting-state fMRI scanning at three time points: diagnosis (M0, pre-adjuvant treatment), at least 1 month (M1), and 7 months (M7) after treatment. The results indicated deficits in cognitive health of breast cancer patients immediately after chemotherapy that improved over time. This psychological trajectory was paralleled by a disruption and later recovery of resting-state functional connectivity, mostly in the parietal and frontal brain regions. The functional connectivity alteration pattern seems to be a separable treatment symptom from the decreased cognitive health. More targeted support for patients should be developed to ameliorate these multi-faceted side effects of chemotherapy treatment on neural functioning and cognitive health.

neuroscience↗

bioRxiv2018

Interhemispheric Integration for Complex Behaviors, Absent the Corpus Callosum in Normal Ontogeny

Functional homotopy, or synchronous spontaneous activity between symmetric, contralateral brain regions, is a fundamental characteristic of the mammalian brains functional architecture(1-6). In mammals, functional homotopy may be predominantly mediated by the corpus callosum (CC), a white matter structure thought to balance the interhemispheric coordination and hemispheric specialization critical for many complex brain functions, including lateralized human language abilities(7, 8). The CC first emerged with the Eutherian (placental) mammals ~160 MYA and is not found in other vertebrates(9, 10). Despite this, other vertebrates also exhibit complex brain functions requiring bilateral integration and lateralization(11). For example, much as humans acquire speech, the zebra finch (Taeniopygia guttata) songbird learns to sing from tutors and must balance hemispheric specialization(12) with interhemispheric coordination to successfully learn and produce song(13). We therefore tested whether the zebra finch brain also exhibits functional homotopy despite lacking the CC. Implementing custom resting-state fMRI (rs-fMRI) functional connectivity (FC) analyses, we demonstrate widespread functional homotopy between pairs of contralateral brain regions required for learned song but which lack direct anatomical projections (i.e., structural connectivity; SC). We believe this is the first demonstration of functional homotopy in a non-Eutherian vertebrate; however, it is unlikely to be the only instance of it. The remarkable congruence between functional homotopy in the zebra finch and Eutherian brains indicates that alternative mechanisms must exist for balanced interhemispheric coordination in the absence of a CC. This insight may have broad implications for understanding complex, bilateral neural processing across phylogeny and how information is integrated between hemispheres.\n\nSignificance StatementThe mammalian brain exhibits strongly synchronized hemodynamic activity (i.e., functional connectivity) between symmetric, contralateral (i.e., homotopic) brain regions. This pattern is thought to be largely mediated by the corpus callosum (CC), a large white matter tract unique to mammals, which balances interhemispheric coordination and lateralization. Many complex brain functions, including human language, are thought to critically rely upon this balance. Despite lacking the CC, the zebra finch exhibits a song learning process with striking parallels to human speech acquisition, including lateralization and interhemispheric coordination. Using resting-state fMRI, we show that the zebra finch brain exhibits widespread homotopic functional connectivity within a network critical for learned song, suggesting that this symmetrical activity pattern may phylogenetically precede the evolution of the CC.

neuroscience↗