Juan Francisco Martín-Rodríguez

Theory of mind deficits in patients with acquired brain injury: A quantitative review

Impaired theory of mind (ToM) reasoning is considered an underlying cause of social cognition deficits in patients with acquired brain injury (ABI). However, the literature does not agree on the severity of ToM impairment in this clinical population, nor does it coincide on the proper tools for its assessment. In this paper, we use a meta-analytic approach to review 26 studies which compare the performance of ABI patients and healthy controls in four widely-used ToM tasks: first-order belief task, second order belief task, understanding indirect speech (IS) and social faux pas. Overall, patients show moderate to severe ToM impairment. The latter appears in faux pas (effect size=0.70) and understanding IS tasks (ES=0.87), while moderate impairment can be seen in second-order (ES=0.60) and first-order belief tasks (ES=0.52). The severity of ToM impairment was influenced by ratio of patients with frontal lobe lesion, ratio of patients with right hemisphere injury, type of belief task, and heterogeneity of the samples etiology. Our results provide important quantitative evidence on the severity of ToM deficits in the ABI population, while identifying variables that influence these deficits. Implications for basic and clinical neuropsychology are discussed.

Evidence of Cognitive and Neurophysiological Impairment in Patients with Untreated Naive Acromegaly

CONTEXT Recent studies have suggested that long-term exposure to high levels of GH and IGF-I affect brain and cognitive functions. However, very few human studies have challenged this hypothesis. OBJECTIVE The aim of this study is to explore whether GH/IGF-I excess in naive patients with acromegaly alters cognitive functions, particularly memory, and whether these alterations are accompanied by neurophysiological correlates. DESIGN We conducted a comprehensive neuropsychological and neurophysiological exam on 16 naive acromegaly patients and 16 strictly matched healthy controls. Comparative analyses were carried out on major neurocognitive domains (executive functions, visual/verbal memory, attention, visuoconstructive abilities, and verbal fluency) and on quantitative electroencephalogram and low-resolution brain electromagnetic tomography sources. Results were correlated with GH and IGF-I hormone concentrations. RESULTS Short- and long-term memory were the most severely impaired cognitive functions. Moreover, memory performance correlated negatively with GH and IGF-I concentrations. No association was detected between depression and memory impairment, and only a marginal association was found with quality of life. Finally, acromegaly patients showed power attenuation in fast frequency electroencephalogram bands, as well as decreased activity in prefrontal and middle temporal cortices, that was associated to cognitive performance. CONCLUSIONS Results provide evidence of cognitive and neurophysiological impairment, characterized by moderate-to-severe memory impairment and decreased neural activity in specific brain areas. High levels of GH and IGF-I in acromegaly patients could be the basis for these findings.

The hemodynamics of cognitive control: The level of concentration of oxygenated hemoglobin in the superior prefrontal cortex varies as a function of performance in a modified Stroop task

The purpose of this study was to establish the relationship between the hemodynamic response of prefrontal cortex (PFC) and individual differences in cognitive control, as measured by a color-word interference task. Twenty-five healthy volunteers were observed through functional near infrared spectroscopy (fNIRS) while performing a modified Stroop paradigm. Mean concentration levels of oxygenated hemoglobin (oxy-Hb) were correlated with behavioral performance in the conflict task. Those with shorter reaction times had higher levels of oxy-Hb concentration in superior dorsolateral PFC. Our results are the first to show a positive correlation between behavioral performance and oxy-Hb levels in superior dorsolateral PFC in a cognitive conflict task. These results suggest that the availability of oxygen in the superior PFC, possibly linked to an increase in metabolism, may be related to attention level and effectiveness of cognitive control.

Delta–alpha ratio correlates with level of recovery after neurorehabilitation in patients with acquired brain injury

OBJECTIVE To explore the relationship between three QEEG global indexes and their association with functional outcome after neurorehabilitation in non-acute acquired brain injury (ABI) patients (traumatic brain injury and stroke). METHODS Twenty-one adult ABI patients in post-acute phase were studied. Delta-alpha ratio (DAR), Power Ratio Index (PRI) and Mean Brain Symmetry Index (mBSI) were calculated from resting-state EEG taken at admission. These indexes and other clinical variables were correlated with functional recovery achieved after six months of neurorehabilitation. RESULTS DAR showed the highest strength of association with the functional outcome measure (rho=-0.65, P=0.002). The other QEEG indexes and clinical variables showed modest non-significant correlations. A posteriori group analysis showed higher DAR in patients with poor recovery as compared to good recovery patients. CONCLUSIONS Functional recovery after neurorehabilitation appears to be associated with a number of clinical and neurophysiological variables. Among the latter, the ratio between delta and alpha may play a significant role in predicting and monitoring functional rehabilitation outcome. SIGNIFICANCE Neurophysiological assessment of ABI patients may be an important tool in monitoring and predicting outcomes after neurorehabilitation.

The prognostic value of the temporal course of S100β protein in post-acute severe brain injury: A prospective and observational study

Primary objective: To study the predictive capacity of early S100β samples for long-term outcome prediction after severe TBI. Methods and procedures: Eighty-seven patients with severe TBI were studied. Clinical and CT scan were taken at admission. S100β concentration was quantified at admission and 24, 48 and 72 hours post-TBI (days 0, 1, 2 and 3). Outcome was assessed 12 months after discharge using Glasgow Outcome Score (GOS). Results: Significant negative correlations were found between 1-year GOS and S100β concentrations on days 1–3, but not on day 0. Deceased patients showed higher S100β concentration than survivors on days 1–3. Good (GOS = 4–5) vs poor outcome (GOS = 1–3) differed significantly on day 3. Death outcome was independently predicted by day 2 (>2.37 µg l−1), day 3 (>1.41 µg l−1) samples and absence of pupillary reaction. Poor outcome was predicted independently only by pupillary reaction and the 72-hour sample (>1.1 µg l−1), but this predictive model was less satisfactory than the predictive model for death. Conclusions: A temporal profile of S100β release from admission to 72 hours post-TBI is strongly recommended for use in identifying patients at risk of developing a worse outcome. The S100β protein might be an early biomarker for predicting long-term outcome in patients with acute severe TBI.

A clinical profile of memory impairment in humans due to endogenous glucocorticoid excess

Objective  Glucocorticoid excess is commonly related to neuropsychiatric and neurological disorders, with memory impairment typically found among these disorders. The objective of this study is to offer a clinical profile of memory deficits resulting from exposure to chronic stress‐level elevations of endogenous glucocorticoids in patients with Cushings Syndrome (CS).

Efficient learning produces spontaneous neural repetition suppression in prefrontal cortex.

Our study focuses on the physiological effects of repetition on learning and working memory using an adaptation of Lurias Memory Word-Task (LMWT). We assess the hemodynamic response in dorsolateral prefrontal cortex (DLPFC) of 13 healthy subjects while completing LMWT. Free word recalls were acquired at the beginning, middle and end of the task. Behavioral results showed that all subjects could recall the complete word list by the 10th trial, which was considered as successful task accomplishment. We observed an attenuation of stimulus-evoked neural activity in prefrontal neurons. Our findings show that the temporal integration of efficient verbal learning is mediated by a mechanism known as neural repetition suppression (NRS). This mechanism facilitates cortical deactivation in DLPFC once learning is successfully completed. This cortical reorganization is interpreted as a progressive optimization of neural responses to produce a more efficient use of neural circuits. NRS could be considered one of the natural mechanisms involved in the processes of memory learning.

A QEEG index of level of functional dependence for people sustaining acquired brain injury: The Seville Independence Index (SINDI)

Primary objective: To find an easy-to-use, valid and reliable tool for evaluating the level of functional dependence of an individual with brain damage who seeks a diagnosis of his/her functional dependence in daily activities. Methods: Eighty-one patients with acquired brain injury (ABI) in post-acute phase, 40 traumatic brain injury (TBI) and 41 cerebral vascular accident (CVA), were assessed using quantitative electroencephalography (QEEG) and grouped according to the FIM + FAM scale. Discriminant analysis was performed on QEEG variables to obtain a discriminant function with the best discriminative capacity between functionality groups. Results: Discriminant analysis showed classification accuracy of 100% in the training set sample and 75% in an external cross-validation sample; 100% sensitivity and 100% specificity were reached. Coherence measures were the most numerous variables in the function. Conclusions: These results point out that the discriminant function may be a useful tool in objective evaluations of patients seeking a diagnosis of their level of dependence and that it could be included in current functionality assessment protocols.

Neurocognitive function in acromegaly after surgical resection of GH-secreting adenoma versus naïve acromegaly.

Patients with active untreated acromegaly show mild to moderate neurocognitive disorders that are associated to chronic exposure to growth hormone (GH) and insulin-like growth factor (IGF-I) hypersecretion. However, it is unknown whether these disorders improve after controlling GH/IGF-I hypersecretion. The aim of this study was to compare neurocognitive functions of patients who successfully underwent GH-secreting adenoma transsphenoidal surgery (cured patients) with patients with naive acromegaly. In addition, we wanted to determine the impact of different clinical and biochemical variables on neurocognitive status in patients with active disease and after long-term cure. A battery of six standardized neuropsychological tests assessed attention, memory and executive functioning. In addition, a quantitative electroencephalography with Low-Resolution Electromagnetic Tomography (LORETA) solution was performed to obtain information about the neurophysiological state of the patients. Neurocognitive data was compared to that of a healthy control group. Multiple linear regression analysis was also conducted using clinical and hormonal parameters to obtain a set of independent predictors of neurocognitive state before and after cure. Both groups of patients scored significantly poorer than the healthy controls on memory tests, especially those assessing visual and verbal recall. Patients with cured acromegaly did not obtain better cognitive measures than naïve patients. Furthermore memory deficits were associated with decreased beta activity in left medial temporal cortex in both groups of patients. Regression analysis showed longer duration of untreated acromegaly was associated with more severe neurocognitive complications, regardless of the diagnostic group, whereas GH levels at the time of assessment was related to neurocognitive outcome only in naïve patients. Longer duration of post-operative biochemical remission of acromegaly was associated with better neurocognitive state. Overall, this data suggests that the effects of chronic exposure to GH/IGF-I hypersecretion could have long-term effects on brain functions.

Budget impact of using midnight salivary cortisol in the diagnosis of hypercortisolism

BACKGROUND A single midnight serum cortisol (MSC) test has been reported to possess the best sensitivity and specificity for diagnosing Cushings syndrome (CS). However, this test requires patient hospitalization, making it costly. This paper aims to compare the hospital budget impact and accuracy of using midnight salivary cortisol (MSVC), as opposed to MSC, in the diagnosis of hypercortisolism. METHODS 77 patients with at least two high urinary free cortisol (UFC) values (>360 nmol/24 h) were selected from 611 patients with clinical symptoms of CS. The costs of the method to confirm the diagnosis of hypercortisolism was calculated comparing Option A using MSC (UFCx2, low-dose dexamethasone suppression test [LDDST]) that requires patient hospitalization versus Option B using MSVC (UFCx2, LDDST) in which the evaluation is done outside the Hospital. A budget impact analysis for one year was developed, and a sensitivity analysis in different scenarios was performed. Reproducibility and diagnostic performance of MSVC and MSC were also measured. RESULTS Salivary cortisol is a sound analytical method for evaluating free serum cortisol due to its classification accuracy, good imprecision, linearity, and stability. AUC(ROC) comparison between MSVC and MSC shows no significant differences. The substitution of the MSC for MSVC in our hospital could save between €16,762 and €132,804 in one year. CONCLUSIONS The use of MSVC in the diagnosis of hypercortisolism can result in a substantial decrease in the budget impact, without losing diagnosis accuracy and reliability, a significant advantage considering the current emphasis on reducing the financial burden of health care.