Objective The thalamus and cerebral cortex are connected via topographically organized, reciprocal connections. Previous studies revealed thalamic abnormalities in schizophrenia; however, it is not known if thalamocortical networks are differentially affected in the disorder. To explore this possibility, we examined functional connectivity in intrinsic low frequency blood-oxygen-level-dependent (BOLD) signal fluctuations between major divisions of the cortex and thalamus using resting-state functional magnetic resonance imaging. Method 77 healthy subjects and 62 patients with schizophrenia underwent resting-state fMRI. To identify functional subdivisions of the thalamus, we parceled the cortex into six regions-of-interest; prefrontal, motor, somatosensory, temporal, posterior parietal, and occipital cortex. Mean BOLD time-series was extracted from each of the regions-of-interest and entered into a seed-based functional connectivity analysis. Results Consistent with prior reports, activity in distinct cortical areas correlated with specific, largely non-overlapping regions of the thalamus in both healthy subjects and schizophrenia patients. Direct comparison between groups revealed reduced prefrontal-thalamic connectivity and increased motor/somatosensory-thalamic connectivity in schizophrenia. The changes in connectivity were unrelated to local grey matter content within the thalamus and antipsychotic medication dosage. No differences were observed in temporal, posterior parietal, and occipital cortex connectivity with the thalamus. Conclusions This study establishes differential abnormalities of thalamocortical networks in schizophrenia. The etiology of schizophrenia may disrupt the development of prefrontal-thalamic connectivity and refinement of somatomotor connectivity with the thalamus that occurs during brain maturation.

Damage to the corticospinal tract is widely studied following unilateral subcortical stroke, whereas less is known about changes to other sensorimotor pathways. This may be due to the fact that many studies investigated morphological changes in the brain, where the majority of descending and ascending brain pathways are overlapping, and did not investigate the brainstem where they separate. Moreover, these pathways continue passing through separate regions in the spinal cord. Here, using a high-resolution structural MRI of both the brainstem and the cervical spinal cord, we were able to identify a number of microstructurally altered pathways, in addition to the corticospinal tract, post stroke. Moreover, decreases in ipsi-lesional corticospinal tract integrity and increases in contra-lesional medial reticulospinal tract integrity were correlated with motor impairment severity in individuals with stroke.

Quantitative spinal cord (SC) magnetic resonance imaging (MRI) is fraught with challenges, among which is the lack of standardized imaging protocols. Here we present a prospectively harmonized quantitative MRI protocol, which we refer to as the spine generic protocol, for the three main 3T MRI vendors: GE, Philips and Siemens. The protocol provides valuable metrics for assessing SC macrostructural and microstructural integrity: T1-weighted and T2-weighted imaging for SC cross-sectional area (CSA) computation, multi-echo gradient echo for gray matter CSA, as well as magnetization transfer and diffusion weighted imaging for assessing white matter microstructure. The spine generic protocol was used to acquire data across 42 centers in 260 healthy subjects, as detailed in the companion paper [REF-DATA]. The spine generic protocol is open-access and its latest version can be found at: https://spinalcordmri.org/protocols. The protocol will serve as a valuable starting point for researchers and clinicians implementing new SC imaging initiatives. Note to the reviewer/editor/publisher: the companion paper is referred to as [REF-DATA]6/52 121 122dealing with cervical myelopathy and MS populations. Applications of the MethodThe proposed protocol is not geared towards a specific disease and it is suitable for imaging WM pathology (demyelination and Wallerian degeneration via axon/myelin-sensitive 122 https://mssociety.ca/about-ms-research/about-our-research-program/research-we-fund/canadian-prospect ive-cohort-study-to-understand-progression-in-ms-canproco 121 https://www.wingsforlife.com/us/research/imaging-spinal-cord-injury-and-assessing-its-predictive-value-th e-inspired-study-2675/ 9/52

Schizophrenia has been conceptualized as a disorder of altered brain connectivity (i.e. dysconnectivity). Until relatively recently, it was not feasible to test dysconnectivity hypotheses of schizophrenia in vivo. Resting-state functional magnetic resonance imaging (fMRI) is a powerful tool for mapping functional networks of the brain, such as the default mode network (DMN), and investigating the systems-level pathology of neurological and psychiatric disorders. In this article, we review the latest findings from resting-state fMRI studies on schizophrenia. Despite the wide array of methods used and heterogeneity of patient samples, several tentative conclusions may be drawn from the existing literature. 1) Connectivity of the DMN is altered in schizophrenia. Findings vary across studies; however, a majority of investigations reported hyper-connectivity of the DMN. 2) Resting-state connectivity of the prefrontal cortex (PFC) is reduced in schizophrenia, particularly intra-PFC connectivity. 3) Cortical-subcortical networks, including thalamocortical, frontolimbic, and cortico-cerebellar networks are altered in schizophrenia. 4) Preliminary findings indicate that functional connectivity within auditory/language networks and the basal ganglia is related to specific clinical symptoms, including auditory- verbal hallucinations and delusions. 5) Whole-brain network topology measures based on graph theory indicate that functional brain networks in schizophrenia are characterized by reduced small-worldness, lower degree connectivity of brain hubs, and decreased modularity. 6) Some of the alterations in functional connectivity observed in probands are present in unaffected relatives, raising the possibility that functional dysconnectivity is an endophenotype related to genetic risk for schizophrenia. Combined, these findings provide broad support for dysconnectivity theories of schizophrenia. We conclude our review with a discussion of the limitations of the existing literature and potentially important areas of future research.

Background Processing speed predicts functional outcome and is a potential endophenotype for schizophrenia. Establishing the neural basis of processing speed impairment may inform the treatment and etiology of schizophrenia. Neuroimaging investigations in healthy subjects have linked processing speed to brain anatomical connectivity. However, the relationship between processing speed impairment and white matter integrity in schizophrenia is unclear. Methods Individuals with schizophrenia and healthy subjects underwent diffusion tensor imaging (DTI) and completed a brief neuropsychological assessment that included measures of processing speed, verbal learning, working memory, and executive functioning. Group differences in white matter integrity, inferred from fractional anisotropy (FA), were examined throughout the brain and the hypothesis that processing speed impairment in schizophrenia is mediated by diminished white matter integrity was tested. Results White matter integrity of the corpus callosum, cingulum, superior and inferior frontal gyri, and precuneus was reduced in schizophrenia. Average FA in these regions mediated group differences in processing speed, but not other cognitive domains. Diminished white matter integrity in schizophrenia was accounted for, in large part, by individual differences in processing speed. Conclusions Cognitive impairment in schizophrenia mediated by reduced white matter integrity. This relationship was strongest for processing speed as deficits in working memory, verbal learning, and executive functioning were not mediated by white integrity. Larger sample sizes may be required to detect more subtle mediation effects in these domains. Interventions that preserve white matter integrity or ameliorate white matter disruption may enhance processing speed and functional outcome in schizophrenia.

Key points Ipsilateral‐projecting corticobulbar pathways, originating primarily from secondary motor areas, innervate the proximal and even distal portions, although they branch more extensively at the spinal cord. It is currently unclear to what extent these ipsilateral secondary motor areas and subsequent cortical projections may contribute to hand function following stroke‐induced damage to one hemisphere. In the present study, we provide both structural and functional evidence indicating that individuals increasingly rely on ipsilateral secondary motor areas, although at the detriment of hand function. Increased activity in ipsilateral secondary motor areas was associated with increased involuntary coupling between shoulder abduction and finger flexion, most probably as a result of the low resolution of these pathways, making it increasingly difficult to open the hand. These findings suggest that, although ipsilateral secondary motor areas may support proximal movements, they do not have the capacity to support distal hand function, particularly for hand opening. Abstract Recent findings have shown connections of ipsilateral cortico‐reticulospinal tract (CRST), predominantly originating from secondary motor areas to not only proximal, but also distal muscles of the arm. Following a unilateral stroke, CRST from the ipsilateral side remains intact and thus has been proposed as a possible backup system for post‐stroke rehabilitation even for the hand. We argue that, although CRST from ipsilateral secondary motor areas can provide control for proximal joints, it is insufficient to control either hand or coordinated shoulder and hand movements as a result of its extensive spinal branching compared to contralateral corticospinal tract. To address this issue, we combined magnetic resonance imaging, high‐density EEG, and robotics in 17 individuals with severe chronic hemiparetic stroke and 12 age‐matched controls. We tested for changes in structural morphometry of the sensorimotor cortex and found that individuals with stroke demonstrated higher grey matter density in secondary motor areas ipsilateral to the paretic arm compared to controls. We then measured cortical activity when participants were attempting to generate hand opening either supported on a table or when lifting against a shoulder abduction load. The addition of shoulder abduction during hand opening increased reliance on ipsilateral secondary motor areas in stroke, but not controls. Crucially, the increased use of ipsilateral secondary motor areas was associated with decreased hand opening ability when lifting the arm as a result of involuntary coupling between the shoulder and wrist/finger flexors. Taken together, this evidence implicates a compensatory role for ipsilateral (i.e. contralesional) secondary motor areas post‐stroke, although with no apparent capacity to support hand function.

In a companion paper by Cohen-Adad et al. we introduce the spine generic quantitative MRI protocol that provides valuable metrics for assessing spinal cord macrostructural and microstructural integrity. This protocol was used to acquire a single subject dataset across 19 centers and a multi-subject dataset across 42 centers (for a total of 260 participants), spanning the three main MRI manufacturers: GE, Philips and Siemens. Both datasets are publicly available via git-annex. Data were analysed using the Spinal Cord Toolbox to produce normative values as well as inter/intra-site and inter/intra-manufacturer statistics. Reproducibility for the spine generic protocol was high across sites and manufacturers, with an average inter-site coefficient of variation of less than 5% for all the metrics. Full documentation and results can be found at https://spine-generic.rtfd.io/. The datasets and analysis pipeline will help pave the way towards accessible and reproducible quantitative MRI in the spinal cord.

Processing speed is the most impaired neuropsychological domain in schizophrenia and a robust predictor of functional outcome. Determining the specific cognitive operations underlying processing speed dysfunction and indentifying their neural correlates may assist in developing pro-cognitive interventions. Response selection, the process of mapping stimuli onto motor responses, correlates with neuropsychological tests of processing speed and may contribute to processing speed impairment in schizophrenia. This study investigated the relationship between behavioral and neural measures of response selection, and a neuropsychological index of processing speed in schizophrenia. 26 patients with schizophrenia and 21 healthy subjects underwent fMRI scanning during performance of 2 and 4-choice-reaction time (RT) tasks and completed the Wechsler Adult Intelligence Scale-III (WAIS) Processing Speed Index (PSI). Response selection, defined as RT slowing between 2 and 4-choice RT, was impaired in schizophrenia and correlated with psychometric processing speed. Greater activation of the dorsolateral prefrontal cortex (PFC) was observed in schizophrenia and correlated with poorer WAIS PSI scores. Deficient response selection and abnormal recruitment of the dorsolateral PFC during response selection contribute to processing speed impairment in schizophrenia. Interventions that improve response selection and normalize dorsolateral PFC function may improve processing speed in schizophrenia.