Stop-signal response inhibition in schizophrenia : Behavioural, event-related potential and functional neuroimaging data

Inhibitory control deficits are well documented in schizophrenia, supported by impairment in an established measure of response inhibition, the stop-signal reaction time (SSRT). We investigated the neural basis of this impairment by comparing schizophrenia patients and controls matched for age, sex and education on behavioural, functional magnetic resonance imaging (fMRI) and event-related potential (ERP) indices of stop-signal task performance. Compared to controls, patients exhibited slower SSRT and reduced right inferior frontal gyrus (rIFG) activation, but rIFG activation correlated with SSRT in both groups. Go stimulus and stop-signal ERP components (N1/P3) were smaller in patients, but the peak latencies of stop-signal N1 and P3 were also delayed in patients, indicating impairment early in stop-signal processing. Additionally, response-locked lateralised readiness potentials indicated response preparation was prolonged in patients. An inability to engage rIFG may predicate slowed inhibition in patients, however multiple spatiotemporal irregularities in the networks underpinning stop-signal task performance may contribute to this deficit.

Cerebellar grey-matter deficits, cannabis use and first-episode schizophrenia in adolescents and young adults

Epidemiological data link adolescent cannabis use to psychosis and schizophrenia, but its contribution to schizophrenia neuropathology remains controversial. First-episode schizophrenia (FES) patients show regional cerebral grey- and white-matter changes as well as a distinct pattern of regional grey-matter loss in the vermis of the cerebellum. The cerebellum possesses a high density of cannabinoid type 1 receptors involved in the neuronal diversification of the developing brain. Cannabis abuse may interfere with this process during adolescent brain maturation leading to ‘schizophrenia-like’ cerebellar pathology. Magnetic resonance imaging and cortical pattern matching techniques were used to investigate cerebellar grey and white matter in FES patients with and without a history of cannabis use and non-psychiatric cannabis users. In the latter group we found lifetime dose-dependent regional reduction of grey matter in the right cerebellar lobules and a tendency for more profound grey-matter reduction in lobule III with younger age at onset of cannabis use. The overall regional grey-matter differences in cannabis users were within the normal variability of grey-matter distribution. By contrast, FES subjects had lower total cerebellar grey-matter : total cerebellar volume ratio and marked grey-matter loss in the vermis, pedunculi, flocculi and lobules compared to pair-wise matched healthy control subjects. This pattern and degree of grey-matter loss did not differ from age-matched FES subjects with comorbid cannabis use. Our findings indicate small dose-dependent effects of juvenile cannabis use on cerebellar neuropathology but no evidence of an additional effect of cannabis use on FES cerebellar grey-matter pathology.

Enhancing sense of recovery and self-reflectivity in people with schizophrenia : a pilot study of Metacognitive Narrative Psychotherapy

Objective This study investigated the effectiveness of an innovative, manualized psychotherapy aimed at enhancing recovery and self-experience in people with schizophrenia, Metacognitive Narrative Psychotherapy. Design Treatment effects were assessed using a mixed methodology. Data were quantitatively assessed using a single sample, pre- and post-therapy design and qualitatively assessed using a case-study methodology. Methods Eleven patients diagnosed with schizophrenia received Metacognitive Narrative Psychotherapy over the course of 11 to 26 months. Therapists were seven supervised postgraduate psychology students. On average patients attended 49 sessions over the course of therapy. Patients completed interview-based and self-report measures for general and treatment-specific outcomes at pre-, mid-, and post-treatment. Results Quantitative analyses showed that patients significantly improved on the general outcome of subjective recovery, as well as the treatment-specific outcome of self-reflectivity, with medium to large effect sizes. Case-study evidence also showed improvements for some patients in symptom severity, and narrative coherence and complexity. Conclusions These results are consistent with previous case-study evidence and suggest that this manualized version of Metacognitive Narrative Psychotherapy produces general and approach-specific improvements for people with schizophrenia. Replication is needed to ascertain its effectiveness with a larger sample size and within a controlled design.

Triumphs and tribulations in the psychotherapy of schizophrenia : reflections on a pilot study of metacognitive narrative psychotherapy

Schizophrenia results in a profound disruption of one’s capacity to make sense of mental states, coherently narrate self-experiences, and meaningfully relate to others. While current treatment options for people with schizophrenia tend to be symptom-focused, experience in designing and implementing a study focusing on enhancing sense of self demonstrates the feasibility of developing and implementing models of treatment that prioritize the subjective distress and self-experience of people with schizophrenia. There is emerging research evidence, based upon dialogical theory of self, that posits the potential of people with deficits of self to engage in meaningful therapeutic relationships and work toward greater integrity of self and degrees of recovery. The challenge is to translate these ideas into a research methodology that can be successfully applied within therapeutic contexts with people who meet the diagnostic criteria for schizophrenia. Based upon dialogical theory, we developed a principle-based manual for metacognitive narrative psychotherapy: a psychological approach to the treatment of people with schizophrenia, which aims to enhance metacognitive capacity and ability to narrate self-experiences. Five phases of treatment were identified: (1) developing a therapeutic relationship, (2) eliciting narratives, (3) enhancing metacognitive capacity, (4) enriching narratives, and (5) living enriched stories. Proscribed practices were also identified. We then implemented the manual within a university clinic context. Six therapists were trained to implement the model and, in turn, provided therapy to 11 patients who completed 12 to 24 months of treatment. Participants were assessed on metacognitive capacity, narrative coherence, narrative richness, self-reported recovery, and symptomatology at three points in time over the course of therapy. Contrary to expectations, participants were highly engaged in the therapeutic process, with minimal dropout. Overall, over 75% of participants evidenced improvement in their level of recovery over the course of therapy. The manualization and outcome findings demonstrate the feasibility of applying such interventions to a broader clinical population.

Functional magnetic resonance brain imaging of executive cognitive performance in young first-episode schizophrenia patients and age-matched long-term cannabis users

Converging evidence from epidemiological, clinical and neuropsychological research suggests a link between cannabis use and increased risk of psychosis. Long-term cannabis use has also been related to deficit-like “negative” symptoms and cognitive impairment that resemble some of the clinical and cognitive features of schizophrenia. The current functional brain imaging study investigated the impact of a history of heavy cannabis use on impaired executive function in first-episode schizophrenia patients. Whilst performing the Tower of London task in a magnetic resonance imaging scanner, event-related blood oxygenation level-dependent (BOLD) brain activation was compared between four age and gender-matched groups: 12 first-episode schizophrenia patients; 17 long-term cannabis users; seven cannabis using first-episode schizophrenia patients; and 17 healthy control subjects. BOLD activation was assessed as a function of increasing task difficulty within and between groups as well as the main effects of cannabis use and the diagnosis of schizophrenia. Cannabis users and non-drug using first-episode schizophrenia patients exhibited equivalently reduced dorsolateral prefrontal activation in response to task difficulty. A trend towards additional prefrontal and left superior parietal cortical activation deficits was observed in cannabis-using first-episode schizophrenia patients while a history of cannabis use accounted for increased activation in the visual cortex. Cannabis users and schizophrenia patients fail to adequately activate the dorsolateral prefrontal cortex, thus pointing to a common working memory impairment which is particularly evident in cannabis-using first-episode schizophrenia patients. A history of heavy cannabis use, on the other hand, accounted for increased primary visual processing, suggesting compensatory imagery processing of the task.

Gray matter deficits, mismatch negativity, and outcomes in schizophrenia

Reduced mismatch negativity (MMN) in response to auditory change is a well-established finding in schizophrenia and has been shown to be correlated with impaired daily functioning, rather than with hallmark signs and symptoms of the disorder. In this study, we investigated (1) whether the relationship between reduced MMN and impaired daily functioning is mediated by cortical volume loss in temporal and frontal brain regions in schizophrenia and (2) whether this relationship varies with the type of auditory deviant generating MMN. MMN in response to duration, frequency, and intensity deviants was recorded from 18 schizophrenia subjects and 18 pairwise age- and gender-matched healthy subjects. Patients’ levels of global functioning were rated on the Social and Occupational Functioning Assessment Scale. High-resolution structural magnetic resonance scans were acquired to generate average cerebral cortex and temporal lobe models using cortical pattern matching. This technique allows accurate statistical comparison and averaging of cortical measures across subjects, despite wide variations in gyral patterns. MMN amplitude was reduced in schizophrenia patients and correlated with their impaired day-to-day function level. Only in patients, bilateral gray matter reduction in Heschl’s gyrus, as well as motor and executive regions of the frontal cortex, correlated with reduced MMN amplitude in response to frequency deviants, while reduced gray matter in right Heschl’s gyrus also correlated with reduced MMN to duration deviants. Our findings further support the importance of MMN reduction in schizophrenia by linking frontotemporal cerebral gray matter pathology to an automatically generated event-related potential index of daily functioning.

Symptom correlates of static and dynamic facial affect processing in schizophrenia : evidence of a double dissociation?

Schizophrenia patients have been shown to be compromised in their ability to recognize facial emotion. This deficit has been shown to be related to negative symptoms severity. However, to date, most studies have used static rather than dynamic depictions of faces. Nineteen patients with schizophrenia were compared with seventeen controls on 2 tasks; the first involving the discrimination of facial identity, emotion, and butterfly wings; the second testing emotion recognition using both static and dynamic stimuli. In the first task, the patients performed more poorly than controls for emotion discrimination only, confirming a specific deficit in facial emotion recognition. In the second task, patients performed more poorly in both static and dynamic facial emotion processing. An interesting pattern of associations suggestive of a possible double dissociation emerged in relation to correlations with symptom ratings: high negative symptom ratings were associated with poorer recognition of static displays of emotion, whereas high positive symptom ratings were associated with poorer recognition of dynamic displays of emotion. However, while the strength of associations between negative symptom ratings and accuracy during static and dynamic facial emotion processing was significantly different, those between positive symptom ratings and task performance were not. The results confirm a facial emotion-processing deficit in schizophrenia using more ecologically valid dynamic expressions of emotion. The pattern of findings may reflect differential patterns of cortical dysfunction associated with negative and positive symptoms of schizophrenia in the context of differential neural mechanisms for the processing of static and dynamic displays of facial emotion.

Cerebellar grey matter deficits in first-episode schizophrenia mapped using cortical pattern matching

Cerebellar dysfunction has been proposed to lead to “cognitive dysmetria” in schizophrenia via the cortico-cerebellar-thalamic-cortical circuit, contributing to a range of cognitive and clinical symptoms of the disorder. Here we investigated total cerebellar grey and white matter volumes and cerebellar regional grey matter abnormalities in 13 remitted first-episode schizophrenia patients with less than 2 years’ duration of illness. Patient data were compared to 13 pair-wise age, gender, and handedness-matched healthy volunteers using cortical pattern averaging on high-resolution magnetic resonance images. Total cerebellar volume and total grey matter volumes in first-episode schizophrenia patients did not differ from healthy control subjects, but total cerebellar white matter was increased and total grey to white matter ratios were reduced in patients. Four clusters of cerebellar grey matter reduction were identified: (i) in superior vermis; (ii) in the left lobuli VI; (iii) in right-inferior lobule IX, extending into left lobule IX; and (iv) bilaterally in the areas of lobuli III, peduncle and left flocculus. Grey matter deficits were particularly prominent in right lobuli III and IX, left flocculus and bilateral pedunculi. These cerebellar areas have been implicated in attention control, emotional regulation, social functioning, initiation of smooth pursuit eye movements, eye-blink conditioning, language processing, verbal memory, executive function and the processing of spatial and emotional information. Consistent with common clinical, cognitive, and pathophysiological signs of established illness, our findings demonstrate cerebellar pathology as early as in first-episode schizophrenia.

Repeatability of static load bearing exercises during rehabilitation of individuals with transfemoral amputation fitted with osseointegrated implant

Bone-anchored prostheses, relying on implants to attach the prosthesis directly to the residual skeleton, are the ultimate resort for patients with transfemoral amputations (TFA) experiencing severe socket discomfort. The first patient receiving a bone-anchored prosthesis underwent the surgery in 1990 in the Sahlgrenska University Hospital (Sweden). To date, there are two commercially available implants: OPRA (Integrum, Sweden) and ILP (Orthodynamics, Germany). The key to success to this technique is a firm bone-implant bonding, depending on increasing mechanical stress applied daily during load bearing exercises (LBE). The loading data could be analysed through different biomechanical variables. The intra-tester reliability of these exercises will be presented here. Moreover the effect of increase of loading, axes of application of the load and body weight as well as the difference between force and moment variables will be discussed.

Visual rehabilitation in low-moderate keratoconus : intracorneal ring segment implantation followed by same-day topography-guided photorefractive keratectomy and collagen cross linking

AIM: To present the results of same-day topography-guided photorefractive keratectomy (TG-PRK) and corneal collagen crosslinking (CXL) after previous intrastromal corneal ring segment (ISCR) implantation for keratoconus. METHODS: An experimental clinical study on twenty-one eyes of 19 patients aged, 27.1±6.6 years (range: 19 – 43 years), with low to moderate keratoconus who were selected to undergo customized TG-PRK immediately followed by same-day CXL, 9 months after ISCR implantation in a university ophthalmology clinic. Refraction, uncorrected (UDVA) and corrected distance visual acuities (CDVA), keratometry (K) values, central corneal thickness (CCT) and coma were assessed 3 months after TG/PRK and CXL. RESULTS: After TG-PRK/CXL: the mean UDVA (logMAR) improved significantly from 0.66±0.41 to 0.20±0.25 (P<0.05); K flat value decreased from: 48.44±3.66 D to 43.71±1.95 D; K steep value decreased from 45.61±2.40 D to 41.56±2.05D; K average also decreased from 42.42±2.07 D to 47.00±2.66 D (P<0.05 for all). The mean sphere and cylinder decreased significantly post-surgery from, -3.10±2.99 D to -0.11±0.93 D and from, -3.68±1.53 to -1.11±0.75D respectively, while the CDVA, CCT and coma showed no significant changes. Compared to post-ISCR, significant reductions (P ˂ 0.05 or all) in all K-values, sphere and cylinder were observed after TG-PRK/CXL. CONCLUSION: Same-day combined topography-guided PRK and corneal crosslinking following placement of ICRS is a safe and potentially effective option in treating low-moderate keratoconus. It significantly improved all visual acuity, reduced keratometry, sphere and astigmatism, but caused no change in central corneal thickness and coma.

Reduced motor facilitation during action observation in schizophrenia : a mirror neuron deficit?

Impairments in social cognitive functioning are well documented in schizophrenia, however the neural basis of these deficits is unclear. A recent explanatory model of social cognition centers upon the activity of mirror neurons, which are cortical brain cells that become active during both the performance and observation of behavior. Here, we test for the first time whether mirror neuron functioning is reduced in schizophrenia. Fifteen individuals with schizophrenia or schizoaffective disorder and fifteen healthy controls completed a transcranial magnetic stimulation (TMS) experiment designed to assess mirror neuron activation. While patients demonstrated no abnormalities in cortical excitability, motor facilitation during action observation, putatively reflecting mirror neuron activity, was reduced in schizophrenia. Dysfunction within the mirror neuron system may contribute to the pathophysiology of schizophrenia.

Patients Undergoing Subacute Physical Rehabilitation following an Acute Hospital Admission Demonstrated Improvement in Cognitive Functional Task Independence

Objective. This study investigated cognitive functioning among older adults with physical debility not attributable to an acute injury or neurological condition who were receiving subacute inpatient physical rehabilitation. Design. A cohort investigation with assessments at admission and discharge. Setting. Three geriatric rehabilitation hospital wards. Participants. Consecutive rehabilitation admissions () following acute hospitalization (study criteria excluded orthopaedic, neurological, or amputation admissions). Intervention. Usual rehabilitation care. Measurements. The Functional Independence Measure (FIM) Cognitive and Motor items. Results. A total of 704 (86.5%) participants (mean age = 76.5 years) completed both assessments. Significant improvement in FIM Cognitive items (-score range 3.93–8.74, all ) and FIM Cognitive total score (-score = 9.12, ) occurred, in addition to improvement in FIM Motor performance. A moderate positive correlation existed between change in Motor and Cognitive scores (Spearman’s rho = 0.41). Generalized linear modelling indicated that better cognition at admission (coefficient = 0.398, ) and younger age (coefficient = −0.280, ) were predictive of improvement in Motor performance. Younger age (coefficient = −0.049, ) was predictive of improvement in FIM Cognitive score. Conclusions. Improvement in cognitive functioning was observed in addition to motor function improvement among this population. Causal links cannot be drawn without further research.

Prevalence of active foot disease and foot disease risk factors in a subacute inpatient rehabilitation facility: a cross-sectional prevalence study

Background Australian subacute inpatient rehabilitation facilities face significant challenges from the ageing population and the increasing burden of chronic disease. Foot disease complications are a negative consequence of many chronic diseases. With the rapid expansion of subacute rehabilitation inpatient services, it seems imperative to investigate the prevalence of foot disease and foot disease risk factors in this population. The primary aim of this cross-sectional study was to determine the prevalence of active foot disease and foot disease risk factors in a subacute inpatient rehabilitation facility. Methods Eligible participants were all adults admitted at least overnight into a large Australian subacute inpatient rehabilitation facility over two different four week periods. Consenting participants underwent a short non-invasive foot examination by a podiatrist utilising the validated Queensland Health High Risk Foot Form to collect data on age, sex, medical co-morbidity history, foot disease risk factor history and clinically diagnosed foot disease complications and foot disease risk factors. Descriptive statistics were used to determine the prevalence of clinically diagnosed foot disease complications, foot disease risk factors and groups of foot disease risk factors. Logistic regression analyses were used to investigate any associations between defined explanatory variables and appropriate foot disease outcome variables. Results Overall, 85 (88%) of 97 people admitted to the facility during the study periods consented; mean age 80 (±9) years and 71% were female. The prevalence (95% confidence interval) of participants with active foot disease was 11.8% (6.3 – 20.5), 32.9% (23.9 – 43.5) had multiple foot disease risk factors, and overall, 56.5% (45.9 – 66.5) had at least one foot disease risk factor. A self-reported history of peripheral neuropathy diagnosis was independently associated with having multiple foot disease risk factors (OR 13.504, p = 0.001). Conclusion This study highlights the potential significance of the burden of foot disease in subacute inpatient rehabilitation facilities. One in eight subacute inpatients were admitted with active foot disease and one in two with at least one foot disease risk factor in this study. It is recommended that further multi-site studies and management guidelines are required to address the foot disease burden in subacute inpatient rehabilitation facilities. Keywords: Subacute; Inpatient; Foot; Complication; Prevalence