Functional reorganization during the recovery of contralesional target selection deficits after prefrontal cortex lesions in macaque monkeys

© 2019 The Authors Visual extinction has been characterized by the failure to respond to a visual stimulus in the contralesional hemifield when presented simultaneously with an ipsilesional stimulus (Corbetta and Shulman, 2011). Unilateral damage to the macaque frontoparietal cortex commonly leads to deficits in contralesional target selection that resemble visual extinction. Recently, we showed that macaque monkeys with unilateral lesions in the caudal prefrontal cortex (PFC) exhibited contralesional target selection deficits that recovered over 2–4 months (Adam et al., 2019). Here, we investigated the longitudinal changes in functional connectivity (FC) of the frontoparietal network after a small or large right caudal PFC lesion in four macaque monkeys. We collected ultra-high field resting-state fMRI at 7-T before the lesion and at weeks 1–16 post-lesion and compared the functional data with behavioural performance on a free-choice saccade task. We found that the pattern of frontoparietal network FC changes depended on lesion size, such that the recovery of contralesional extinction was associated with an initial increase in network FC that returned to baseline in the two small lesion monkeys, whereas FC continued to increase throughout recovery in the two monkeys with a larger lesion. We also found that the FC between contralesional dorsolateral PFC and ipsilesional parietal cortex correlated with behavioural recovery and that the contralesional dorsolateral PFC showed increasing degree centrality with the frontoparietal network. These findings suggest that both the contralesional and ipsilesional hemispheres play an important role in the recovery of function. Importantly, optimal compensation after large PFC lesions may require greater recruitment of distant and intact areas of the frontoparietal network, whereas recovery from smaller lesions was supported by a normalization of the functional network

Structural alterations in cortical and thalamocortical white matter tracts after recovery from prefrontal cortex lesions in macaques

Unilateral damage to the frontoparietal network typically impairs saccade target selection within the contralesional visual hemifield. Severity of deficits and the degree of recovery have been associated with widespread network dysfunction, yet it is not clear how these behavioural and functional brain changes relate with the underlying structural white matter tracts. Here, we investigated whether recovery after unilateral prefrontal cortex (PFC) lesions was associated with changes in white matter microstructure across large-scale frontoparietal cortical and thalamocortical networks. Diffusion-weighted imaging was acquired in four male rhesus macaques at pre-lesion, week 1, and week 8-16 post-lesion when target selection deficits largely recovered. Probabilistic tractography was used to reconstruct cortical frontoparietal fiber tracts, including the superior longitudinal fasciculus (SLF) and transcallosal fibers connecting the PFC or posterior parietal cortex (PPC), as well as thalamocortical fiber tracts connecting the PFC and PPC to thalamic nuclei. We found that the two animals with small PFC lesions showed increased fractional anisotropy in both cortical and thalamocortical fiber tracts when behaviour had recovered. However, we found that fractional anisotropy decreased in cortical frontoparietal tracts after larger PFC lesions yet increased in some thalamocortical tracts at the time of behavioural recovery. These findings indicate that behavioural recovery after small PFC lesions may be supported by both cortical and subcortical areas, whereas larger PFC lesions may have induced widespread structural damage and hindered compensatory remodeling in the cortical frontoparietal network

Intrinsic functional boundaries of lateral frontal cortex in the common marmoset monkey

© 2019 the authors. The common marmoset (Callithrix jacchus) is a small New World primate species that has been recently targeted as a potentially powerful preclinical model of human prefrontal cortex dysfunction. Although the structural boundaries of frontal cortex were described in marmosets at the start of the 20th century (Brodmann, 1909) and refined more recently (Paxinos et al., 2012), the broad functional boundaries of marmoset frontal cortex have yet to be established. In this study, we sought to functionally derive boundaries of the marmoset lateral frontal cortex (LFC) using ultra-high field (9.4 T) resting-state functional magnetic resonance imaging (RS-fMRI). We collectedRS-fMRIdatainseven(fourfemales,threemales)lightlyanesthetizedmarmosetsandusedadata-drivenhierarchicalclustering approach to derive subdivisions of the LFC based on intrinsic functional connectivity. We then conducted seed-based analyses to assess the functional connectivity between these clusters and the rest of the brain. The results demonstrated seven distinct functional clusters withintheLFC.Thefunctionalconnectivitypatternsoftheseclusterswiththerestofthebrainwerealsofoundtobedistinctandorganized along a rostrocaudal gradient, consonant with those found in humans and macaques. Overall, these results support the view that marmosets are a promising preclinical modeling species for studying LFC dysfunction related to neuropsychiatric or neurodegenerative human brain diseases

Differential Effects of Viewpoint on Object-Driven Activation in Dorsal and Ventral Streams

AbstractUsing fMRI, we showed that an area in the ventral temporo-occipital cortex (area vTO), which is part of the human homolog of the ventral stream of visual processing, exhibited priming for both identical and depth-rotated images of objects. This pattern of activation in area vTO corresponded to performance in a behavioral matching task. An area in the caudal part of the intraparietal sulcus (area cIPS) also showed priming, but only with identical images of objects. This dorsal-stream area treated rotated images as new objects. The difference in the pattern of priming-related activation in the two areas may reflect the respective roles of the ventral and dorsal streams in object recognition and object-directed action

Effects of phase regression on high-resolution functional MRI of the primary visual cortex

High-resolution functional MRI studies have become a powerful tool to non-invasively probe the sub-millimeter functional organization of the human cortex. Advances in MR hardware, imaging techniques and sophisticated post-processing methods have allowed high resolution fMRI to be used in both the clinical and academic neurosciences. However, consensus within the community regarding the use of gradient echo (GE) or spin echo (SE) based acquisition remains largely divided. On one hand, GE provides a high temporal signal-to-noise ratio (tSNR) technique sensitive to both the macro- and micro-vascular signal while SE based methods are more specific to microvasculature but suffer from lower tSNR and specific absorption rate limitations, especially at high field and with short repetition times. Fortunately, the phase of the GE-EPI signal is sensitive to vessel size and this provides a potential avenue to reduce the macrovascular weighting of the signal (phase regression, Menon 2002). In order to determine the efficacy of this technique at high-resolution, phase regression was applied to GE-EPI timeseries and compared to SE-EPI to determine if GE-EPI\u27s specificity to the microvascular compartment improved. To do this, functional data was collected from seven subjects on a neuro-optimized 7 T system at 800 μm isotropic resolution with both GE-EPI and SE-EPI while observing an 8 Hz contrast reversing checkerboard. Phase data from the GE-EPI was used to create a microvasculature-weighted time series (GE-EPI-PR). Anatomical imaging (MP2RAGE) was also collected to allow for surface segmentation so that the functional results could be projected onto a surface. A multi-echo gradient echo sequence was collected and used to identify venous vasculature. The GE-EPI-PR surface activation maps showed a high qualitative similarity with SE-EPI and also produced laminar activity profiles similar to SE-EPI. When the GE-EPI and GE-EPI-PR distributions were compared to SE-EPI it was shown that GE-EPI-PR had similar distribution characteristics to SE-EPI (p \u3c 0.05) across the top 60% of cortex. Furthermore, it was shown that GE-EPI-PR has a higher contrast-to-noise ratio (0.5 ± 0.2, mean ± std. dev. across layers) than SE-EPI (0.27 ± 0.07) demonstrating the technique has higher sensitivity than SE-EPI. Taken together this evidence suggests phase regression is a useful method in low SNR studies such as high-resolution fMRI

Effects of MP2RAGE B\u3csub\u3e1\u3c/sub\u3e\u3csup\u3e+\u3c/sup\u3e sensitivity on inter-site T\u3csub\u3e1\u3c/sub\u3e reproducibility and hippocampal morphometry at 7T

Most neuroanatomical studies are based on T -weighted MR images, whose intensity profiles are not solely determined by the tissue\u27s longitudinal relaxation times (T ), but also affected by varying non-T contributions, hampering data reproducibility. In contrast, quantitative imaging using the MP2RAGE sequence, for example, allows direct characterization of the brain based on the tissue property of interest. Combined with 7 Tesla (7T) MRI, this offers unique opportunities to obtain robust high-resolution brain data characterized by a high reproducibility, sensitivity and specificity. However, specific MP2RAGE parameter choices – e.g., to emphasize intracortical myelin-dependent contrast variations – can substantially impact image quality and cortical analyses through remnants of B -related intensity variations, as illustrated in our previous work. To follow up on this: we (1) validate this protocol effect using a dataset acquired with a particularly B insensitive set of MP2RAGE parameters combined with parallel transmission excitation; and (2) extend our analyses to evaluate the effects on hippocampal morphometry. The latter remained unexplored initially, but can provide important insights related to generalizability and reproducibility of neurodegenerative research using 7T MRI. We confirm that B inhomogeneities have a considerably variable effect on cortical T estimates, as well as on hippocampal morphometry depending on the MP2RAGE setup. While T differed substantially across datasets initially, we show the inter-site T comparability improves after correcting for the spatially varying B field using a separately acquired Sa2RAGE B map. Finally, removal of B residuals affects hippocampal volumetry and boundary definitions, particularly near structures characterized by strong intensity changes (e.g. cerebral spinal fluid). Taken together, we show that the choice of MP2RAGE parameters can impact T comparability across sites and present evidence that hippocampal segmentation results are modulated by B inhomogeneities. This calls for careful (1) consideration of sequence parameters when setting acquisition protocols, as well as (2) acquisition of a B map to correct MP2RAGE data for potential B variations to allow comparison across datasets. 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 + + + + + + + +

Face selective patches in marmoset frontal cortex

© 2020, The Author(s). In humans and macaque monkeys, socially relevant face processing is accomplished via a distributed functional network that includes specialized patches in frontal cortex. It is unclear whether a similar network exists in New World primates, who diverged ~35 million years from Old World primates. The common marmoset is a New World primate species ideally placed to address this question given their complex social repertoire. Here, we demonstrate the existence of a putative high-level face processing network in marmosets. Like Old World primates, marmosets show differential activation in anterior cingulate and lateral prefrontal cortices while they view socially relevant videos of marmoset faces. We corroborate the locations of these frontal regions by demonstrating functional and structural connectivity between these regions and temporal lobe face patches. Given the evolutionary separation between macaques and marmosets, our results suggest this frontal network specialized for social face processing predates the separation between Platyrrhini and Catarrhini

Resting State and Diffusion Neuroimaging Predictors of Clinical Improvements Following Constraint-Induced Movement Therapy in Children With Hemiplegic Cerebral Palsy.

The aim was to identify neuroimaging predictors of clinical improvements following constraint-induced movement therapy. Resting state functional magnetic resonance and diffusion tensor imaging data was acquired in 7 children with hemiplegic cerebral palsy. Clinical and magnetic resonance imaging (MRI) data were acquired at baseline and 1 month later following a 3-week constraint therapy regimen. A more negative baseline laterality index characterizing an atypical unilateral sensorimotor resting state network significantly correlated with an improvement in the Canadian Occupational Performance Measure score (r = -0.81, P = .03). A more unilateral network with decreased activity in the affected hemisphere was associated with greater improvements in clinical scores. Higher mean diffusivity in the posterior limb of the internal capsule of the affect tract correlated significantly with improvements in the Jebsen-Taylor score (r = -0.83, P = .02). Children with more compromised networks and tracts improved the most following constraint therapy