Cortico-cerebellar functional connectivity and sequencing of movements in schizophrenia

<p>Abstract</p> <p>Background</p> <p>Abnormal execution of several movements in a sequence is a frequent finding in schizophrenia. Successful performance of such motor acts requires correct integration of cortico-subcortical processes, particularly those related to cerebellar functions. Abnormal connectivity between cortical and cerebellar regions with resulting cognitive dysmetria has been proposed as the core dysfunction behind many signs and symptoms of schizophrenia. The aim of the present study was to assess if these proposed abnormalities in connectivity are a unifying feature of schizophrenia, or, rather, reflect a specific symptom domain of a heterogeneous disease. We predicted that abnormal functional connectivity between the motor cortex and cerebellum would be linked with abnormal performance of movement sequencing.</p> <p>Methods</p> <p>We examined 24 schizophrenia patients (SCH) and 24 age-, sex-, and handedness-matched healthy controls (HC) using fMRI during a modified finger-tapping task. The ability to perform movement sequencing was tested using the Neurological Evaluation Scale (NES). The subjects were categorized into two groups, with (SQ+) and without (SQ-) movement sequencing abnormalities, according to the NES-SQ score. The effects of diagnosis and movement sequencing abnormalities on the functional connectivity parameters between the motor cortex and cerebellum (MC-CRBL) and the supplementary motor cortex and cerebellum (SMA-CRBL) activated during the motor task were analyzed.</p> <p>Results</p> <p>We found no effect of diagnosis on the functional connectivity measures. There was, however, a significant effect on the SQ group: SQ + patients showed a lower level of MC-CRBL connectivity than SQ- patients and healthy controls. Moreover, the level of MC-CRBL and SMA-CRBL negatively correlated with the magnitude of NES-SQ abnormalities, but with no other NES domain.</p> <p>Conclusions</p> <p>Abnormal cortico-cerebellar functional connectivity during the execution of a motor task is linked with movement sequencing abnormalities in schizophrenia, but not with the diagnosis of schizophrenia per se. It seems that specific patterns of inter-regional connectivity are linked with corresponding signs and symptoms of clinically heterogeneous conditions such as schizophrenia.</p

Diffusion tensor imaging of frontal lobe white matter tracts in schizophrenia

We acquired diffusion tensor and structural MRI images on 103 patients with schizophrenia and 41 age-matched normal controls. The vector data was used to trace tracts from a region of interest in the anterior limb of the internal capsule to the prefrontal cortex. Patients with schizophrenia had tract paths that were significantly shorter in length from the center of internal capsule to prefrontal white matter. These tracts, the anterior thalamic radiations, are important in frontal-striatal-thalamic pathways. These results are consistent with findings of smaller size of the anterior limb of the internal capsule in patients with schizophrenia, diffusion tensor anisotropy decreases in frontal white matter in schizophrenia and hypothesized disruption of the frontal-striatal-thalamic pathway system

Fractional Anisotropic Changes of Corpus Callosum Associated with Antipsychotic Treatment in First-Episode Antipsychotic Drug-Naive Patients with Schizophrenia

WOS: 000390418700002Objective: Schizophrenia involves white matter abnormalities that might have a central role in the pathophysiology. Abnormal brain connectivity especially in prefrontal and temporal heteromodal cortex has been suggested as the leading structural impairment in patients with schizophrenia. In this study we examined the relationship between potential white matter changes and clinical response, as well as associations with antipsychotic treatment follow-up. Methods: 18 first-episode schizophrenia (FES) patients were recruited from the outpatient unit of the GATA (Gulhane Military Medical Academy) Haydarpasa Research and Training Hospital, between June 2009-February 2010. Fourteen patients with FES were recruited, and 16 healthy control subjects were recruited from the community. Diffusion tensor MRI (DT-MRI) was obtained from participants at baseline and after 4 weeks of standard antipsychotic treatment. A color-coded fractional anisotropy map for each 11 patient was extracted from the 4-week follow-up and the baseline splenium and genu FA measurements. According to Basser and others major eigenvector linear maps were transformed into the color-coded maps. Differences in Positive and Negative Syndrome Scale (PANSS) scores and Brief Psychiatric Rating Scale (BPRS) scores between baseline and follow up were also evaluated. Results: In this study; in the FES patients, both genu FA (p=0.001) and the splenium FA (p=0.013) values were statistically significantly lower than the healthy control group. There were mild FA increases respectively genu and splenium (p=0.533, p=0.318) in the FES patients after the treatment. But the FA changes did not correlate with the changes in clinical symptoms. A negative, moderate, statistically significant correlation (Pearson's r=-0.569, p=0.034) was found between baseline splenium FA values and BPRS scores. The duration of illness prior to treatment was negatively, weak, statistically non-significantly correlated (r=-0.066; p=0.846) between baseline and follow-up splenium FA changes. Conclusions: The reduced mean Callosal FA (CFA) values might indicate myelination defects and problems in axonal transport. The existence of white matter changes even in first episode drug-naive schizophrenia patients supports the view that these problems occurs in earlier stages of development. Although the callosal FA changes did not correlate with symptom improvement or the dose of antipsychotic medication, there was a mild increase in follow-up FA measurements. These findings show that CC which is the main conduit of interhemispheric connection is affected distinctly in patients with schizophrenia. Further collaborative studies are needed to clarify the potential long-term effects of antipsychotics on white matter microstructure and also its reversibility

In reply to Drs Lipman and Hackett

We appreciate the discourse from Drs Lipman and Hackett, value their insights, and welcome the opportunity to discuss our study

Prophylactic acetaminophen or ibuprofen result in equivalent acute mountain sickness incidence at high altitude: a prospective randomized trial

Objective Recent trials have demonstrated the usefulness of ibuprofen in the prevention of acute mountain sickness (AMS), yet the proposed anti-inflammatory mechanism remains unconfirmed. Acetaminophen and ibuprofen were tested for AMS prevention. We hypothesized that a greater clinical effect would be seen from ibuprofen due to its anti-inflammatory effects compared with acetaminophen’s mechanism of possible symptom reduction by predominantly mediating nociception in the brain. Methods A double-blind, randomized trial was conducted testing acetaminophen vs ibuprofen for the prevention of AMS. A total of 332 non-Nepali participants were recruited at Pheriche (4371 m) and Dingboche (4410 m) on the Everest Base Camp trek. The participants were randomized to either acetaminophen 1000 mg or ibuprofen 600 mg 3 times a day until they reached Lobuche (4940 m), where they were reassessed. The primary outcome was AMS incidence measured by the Lake Louise Questionnaire score. Results Data from 225 participants who met inclusion criteria were analyzed. Twenty-five participants (22.1%) in the acetaminophen group and 18 (16.1%) in the ibuprofen group developed AMS (P = .235). The combined AMS incidence was 19.1% (43 participants), 14 percentage points lower than the expected AMS incidence of untreated trekkers in prior studies at this location, suggesting that both interventions reduced the incidence of AMS. Conclusions We found little evidence of any difference between acetaminophen and ibuprofen groups in AMS incidence. This suggests that AMS prevention may be multifactorial, affected by anti-inflammatory inhibition of the arachidonic-acid pathway as well as other analgesic mechanisms that mediate nociception. Additional study is needed