The FreiBurger: a new optotype for P300-based acuity estimation.

PURPOSE: Accurate objective assessment of visual acuity is crucial, particularly in cases of suspected malingering, or when the patient's inability to cooperate makes standard psychophysical acuity tests unreliable. The P300 component of the event-related potentials offers a potential solution and even allows for the use of standard optotypes like the Landolt C. However, low-vision patients with large eccentric visual field defects often struggle to locate the Landolt C gap quickly enough for a P300 to be reliably produced. METHODS: Addressing this challenge, we introduce a novel optotype (the "FreiBurger") with a critical detail that extends through the optotype's center. Two experiments, with 16 and 12 participants, respectively, were conducted. In the first, psychophysical acuity estimates were obtained with both the FreiBurger and the Landolt C. In the second, we tested the performance of the FreiBurger, relative to the Landolt C, in eliciting a P300 with undegraded vision, simulated low vision, and in a simulated combination of low vision and visual field constriction. RESULTS: Comparable psychophysical acuity values (average difference 0.03 logMAR) were obtained for both optotypes. In the P300 recordings, both optotypes produced similar P300 responses under conditions of undegraded vision and low vision. However, with the combination of low vision and constricted visual field, the P300 could only be reliably obtained with the FreiBurger, while the amplitude was drastically reduced with the Landolt C (9.1 µV vs. 2.2 µV; p < 0.0005). CONCLUSION: The new optotype extends the applicability of P300-based acuity estimation to the frequently encountered combination of low vision and constricted visual field, where Landolt C optotypes fail. Although impairments were simulated in the present study, we assume that the advantages of the new optotype will also manifest in patients with such impairments. We furthermore expect the advantages to apply to time-sensitive psychophysical examinations as well.

Integrating a multimodal lifestyle intervention with medical food in prodromal Alzheimer's disease: the MIND-ADmini randomized controlled trial.

BACKGROUND: The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) showed cognitive benefits from a multidomain lifestyle intervention in at-risk older people. The LipiDiDiet trial highlighted benefits of medical food in prodromal Alzheimer's disease (AD). However, the feasibility and impact of multimodal interventions combining lifestyle with medical food in prodromal AD is unclear. METHODS: MIND-ADmini was a 6-month multinational (Sweden, Finland, Germany, France) proof-of-concept randomized controlled trial (RCT). Participants were 60-85 years old, had prodromal AD (International Working Group-1 criteria), and vascular/lifestyle risk factors. The parallel-group RCT had three arms: multimodal lifestyle intervention (nutritional guidance, exercise, cognitive training, vascular/metabolic risk management and social stimulation); multimodal lifestyle intervention + medical food (Fortasyn Connect); and regular health advice/care (control). Participants were randomized 1:1:1 (computer-generated allocation at each site). Outcome evaluators were blinded to randomization. Primary outcome was feasibility of the multimodal intervention, evaluated by recruitment rate during a 6-month recruitment phase, overall adherence in each intervention arm, and 6-month retention rate. Successful adherence was pre-specified as attending ≥ 40% of sessions/domain in ≥ 2/4 domains (lifestyle intervention), and consuming ≥ 60% of the medical food (lifestyle intervention + medical food). The secondary outcomes included adherence/participation to each intervention component and overall adherence to healthy lifestyle changes, measured using a composite score for healthy lifestyle. Cognitive assessments were included as exploratory outcomes, e.g. Clinical Dementia Rating scale. RESULTS: During September 2017-May 2019, 93 individuals were randomized (32 lifestyle intervention, 31 lifestyle + medical food, and 30 control group). Overall recruitment rate was 76.2% (64.8% during the first 6 months). Overall 6-month retention rate was 91.4% (lifestyle intervention 87.5%; lifestyle + medical food 90.3%; control 96.7%). Domain-specific adherence in the lifestyle intervention group was 71.9% to cognitive training, 78.1% exercise, 68.8% nutritional guidance, and 81.3% vascular risk management; and in the lifestyle + medical food group, 90.3% to cognitive training, 87.1% exercise, 80.7% nutritional guidance, 87.1% vascular risk management, and 87.1% medical food. Compared with control, both intervention arms showed healthy diet improvements (ßLifestyle×Time = 1.11, P = 0.038; ßLifestyle+medical food×Time = 1.43, P = 0.007); the lifestyle + medical food group also showed vascular risk reduction (P = 0.043) and less cognitive-functional decline (P < 0.05, exploratory analysis). There were 5 serious adverse events (control group: 1; lifestyle intervention: 3; lifestyle + medical food: 1) unrelated to interventions. CONCLUSIONS: The multidomain lifestyle intervention, alone or combined with medical food, had good feasibility and adherence in prodromal AD. Longer-term cognitive and other health benefits should be further investigated in a larger-scale trial. TRIAL REGISTRATION: ClinicalTrials.gov NCT03249688.

Autobiographical memory in chronic schizophrenia: A follow-up study.

Chronic schizophrenia is a very disabling disease and patient's social integration remains difficult. One important aspect is autobiographical memory (AM) as it is impaired in schizophrenia and highly correlated to patient's outcome, since its closely linked to self and identity. Reduced specificity and lack of details are characteristics of patients' AM, but its longitudinal course in schizophrenia remains unclear. We examined 21 patients who underwent our protocol twice with an interval of 7 years. AM was assessed using a semi-structured interview, covering four periods of life and addressing semantic knowledge and autobiographical episodes as well as their details. The results can be divided into three parts, separating semantic memories, specific autobiographical memories and details describing the latter. While a significant deterioration of semantic AM over time could be revealed, the specificity of the free recalled autobiographical episodes remained rather stable - albeit on a low level. In contrast, unique events were remembered with significantly less details at follow-up than at the first examination. While floor-effects given a relatively small number of unique events have to be considered, semantic AM and episodic details seem to be a valuable target for AM remediation given their further deterioration over time.

Neurological soft signs and cognition in the late course of chronic schizophrenia: a longitudinal study.

Neurological soft signs (NSS) are minor ('soft') neurological abnormalities in sensory and motor performances, which are frequently reported in patients with schizophrenia at any stage of their illness. It has been demonstrated that NSS vary in the clinical course of the disorder: longitudinally NSS decrease in parallel with remission of psychopathological symptoms, an effect which mainly applies to patients with a remitting course. These findings are primarily based on patients with a first episode of the disorder, while the course of NSS in patients with chronic schizophrenia and persisting symptoms is rather unknown. Therefore, we investigated NSS twice in 21 patients with chronic schizophrenia (initial mean duration of illness: 23 ± 11 years) with a mean follow-up interval of 7 years. NSS were evaluated by the Heidelberg Scale, established instruments were used to rate neuropsychological performance and psychopathological symptoms. NSS showed significant increases on the subscales "motor coordination" and "integrative functions", while positive and negative symptoms, including apathy, showed only minor, non-significant changes. Verbal memory, verbal fluency, and cognitive flexibility along with severity of global cognitive deficits demonstrated a significant deterioration. Regression analyses identified executive dysfunction (cognitive flexibility and verbal fluency) at baseline as significant predictors of NSS increase at follow-up. Our findings indicate that NSS deteriorate in the long-term course of chronic schizophrenia. This effect may be accounted for by a decrease of executive functions and logical memory, which can be attributed to premature brain aging.

Neurological soft signs (NSS) and cognitive impairment in chronic schizophrenia.

Recent studies indicate that neurological soft signs (NSS) in schizophrenia are associated with generalized cognitive impairments rather than changes in specific neuropsychological domains. However, the majority of studies solely included first-episode patients or patients with a remitting course and did not consider age, course, education or severity of global cognitive deficits as potential confounding variables. Therefore, we examined NSS with respect to cognitive deficits in chronic schizophrenia, i.e. patients who are particularly vulnerable to both, NSS and cognitive impairments. Eighty patients with chronic schizophrenia (43.36 ±â€¯15a) and 60 healthy controls (47.52 ±â€¯14.8a) matched for age, sex and years of education were examined on the Heidelberg NSS scale and a broad neuropsychological battery including short term, working, logical and autobiographic memory (AM), theory of mind (ToM), psychomotor speed and cognitive flexibility. When contrasted with the controls, patients showed significantly higher NSS scores and impairments in all neuropsychological domains but short-term memory. NSS were significantly associated with all neuropsychological domains considered but short-term memory and semantic AM. Except for episodic AM (which was significantly correlated with NSS in patients only) these correlations applied to both groups and were confirmed when age, years of education and severity of global cognitive deficits (Mini Mental State Examination) were controlled for. Results demonstrate that NSS reflect a rather wide range of cognitive impairments in schizophrenia, which also involves episodic AM and ToM. These associations were not accounted for by age, education or severity of global cognitive deficits and facilitate the clinical usage of NSS as a screening instrument.

Neurophysiological responses to unpleasant stimuli (acute electrical stimulations and emotional pictures) are increased in patients with schizophrenia.

Patients with schizophrenia have often been described as insensitive to nociceptive signals, but objective evidence is sparse. We address this question by combining subjective behavioral and objective neurochemical and neurophysiological measures. The present study involved 21 stabilized and mildly symptomatic patients with schizophrenia and 21 control subjects. We applied electrical stimulations below the pain threshold and assessed sensations of pain and unpleasantness with rating scales, and Somatosensory Evoked Potentials (SEPs/EEG). We also measured attention, two neurochemical stress indices (ACTH/cortisol), and subjective VEPs/EEG responses to visual emotional stimuli. Our results revealed that, subjectively, patients' evaluations do not differ from controls. However, the amplitude of EEG evoked potentials was greater in patients than controls as early as 50 ms after electrical stimulations and beyond one second after visual processing of emotional pictures. Such responses could not be linked to the stress induced by the stimulations, since stress hormone levels were stable. Nor was there a difference between patients and controls in respect of attention performance and tactile sensitivity. Taken together, all indices measured in patients in our study were either heightened or equivalent relative to healthy volunteers.

Disruption of information processing in schizophrenia: The time perspective.

We review studies suggesting time disorders on both automatic and subjective levels in patients with schizophrenia. Patients have difficulty explicitly discriminating between simultaneous and asynchronous events, and ordering events in time. We discuss the relationship between these difficulties and impairments on a more elementary level. We showed that for undetectable stimulus onset asynchronies below 20 ms, neither patients nor controls merge events in time, as previously believed. On the contrary, subjects implicitly distinguish between events even when evaluating them to be simultaneous. Furthermore, controls privilege the last stimulus, whereas patients seem to stay stuck on the first stimulus when asynchronies are sub-threshold. Combining previous results shows this to be true for patients even for asynchronies as short as 8 ms. Moreover, this peculiarity predicts difficulties with detecting asynchronies longer than 50 ms, suggesting an impact on the conscious ability to time events. Difficulties on the subjective level are also correlated with clinical disorganization. The results are interpreted within the framework of predictive coding which can account for an implicit ability to update events. These results complement a range of other results, by suggesting a difficulty with binding information in time as well as space, and by showing that information processing lacks continuity and stability in patients. The time perspective may help bridge the gap between cognitive impairments and clinical symptoms, by showing how the innermost structure of thought and experience is disrupted.

Patients with schizophrenia selectively impaired in temporal order judgments.

The ability to order events in time plays a pervasive role in cognitive functions, but has only rarely been explored in patients with schizophrenia. Results we obtained recently suggested that patients have difficulties following events over time. However, this impairment concerned implicit responses at very short asynchronies, and it is not known whether it generalizes to subjective temporal order judgments. Here, we make a direct comparison between temporal order judgments and simultaneity/asynchrony discrimination in the same patients. Two squares were displayed on the screen either simultaneously or with an asynchrony of 24 to 96ms. In one session 20 patients and 20 controls made a temporal order judgment and in the other they discriminated between simultaneous and asynchronous stimuli. Controls recorded similar performances in the two tasks at asynchronies above 50ms, whereas patients displayed a sizeable impairment in temporal order judgment selectively. This impairment occurred in the easiest conditions, with the largest SOAs (Stimulus Onset Asynchronies) and only in the temporal order judgment. The results are the first evidence that patients with schizophrenia have a selective difficulty determining temporal order, even for asynchronies producing a clear perception of asynchrony. This impairment may mediate difficulties engaging oneself in everyday life events.