Test-retest reliability of spectral parameterization by 1/f characterization using SpecParam.

SpecParam (formally known as FOOOF) allows for the refined measurements of electroencephalography periodic and aperiodic activity, and potentially provides a non-invasive measurement of excitation: inhibition balance. However, little is known about the psychometric properties of this technique. This is integral for understanding the usefulness of SpecParam as a tool to determine differences in measurements of cognitive function, and electroencephalography activity. We used intraclass correlation coefficients to examine the test-retest reliability of parameterized activity across three sessions (90 minutes apart and 30 days later) in 49 healthy young adults at rest with eyes open, eyes closed, and during three eyes closed cognitive tasks including subtraction (Math), music recall (Music), and episodic memory (Memory). Intraclass correlation coefficients were good for the aperiodic exponent and offset (intraclass correlation coefficients > 0.70) and parameterized periodic activity (intraclass correlation coefficients > 0.66 for alpha and beta power, central frequency, and bandwidth) across conditions. Across all three sessions, SpecParam performed poorly in eyes open (40% of participants had poor fits over non-central sites) and had poor test-retest reliability for parameterized periodic activity. SpecParam mostly provides reliable metrics of individual differences in parameterized neural activity. More work is needed to understand the suitability of eyes open resting data for parameterization using SpecParam.

Medication-invariant resting aperiodic and periodic neural activity in Parkinson's disease.

Parkinson's disease (PD) has been associated with greater total power in canonical frequency bands (i.e., alpha, beta) of the resting electroencephalogram (EEG). However, PD has also been associated with a reduction in the proportion of total power across all frequency bands. This discrepancy may be explained by aperiodic activity (exponent and offset) present across all frequency bands. Here, we examined differences in the eyes-open (EO) and eyes-closed (EC) resting EEG of PD participants (N = 26) on and off medication, and age-matched healthy controls (CTL; N = 26). We extracted power from canonical frequency bands using traditional methods (total alpha and beta power) and extracted separate parameters for periodic (parameterized alpha and beta power) and aperiodic activity (exponent and offset). Cluster-based permutation tests over spatial and frequency dimensions indicated that total alpha and beta power, and aperiodic exponent and offset were greater in PD participants, independent of medication status. After removing the exponent and offset, greater alpha power in PD (vs. CTL) was only present in EO recordings and no reliable differences in beta power were observed. Differences between PD and CTL in the resting EEG are likely driven by aperiodic activity, suggestive of greater relative inhibitory neural activity and greater neuronal spiking. Our findings suggest that resting EEG activity in PD is characterized by medication-invariant differences in aperiodic activity which is independent of the increase in alpha power with EO. This highlights the importance of considering aperiodic activity contributions to the neural correlates of brain disorders.

Insomnia moderates the association between psychotic-like experiences and suicidal ideation in a non-clinical population: a network analysis.

Psychotic-like experiences (PLEs) have been associated with poor sleep quality and increased suicide risk. However, the association between PLEs, insomnia and suicide risk has not been thoroughly investigated in prior studies. In this study, we aimed to explore as to whether insomnia moderates the association between PLEs and suicidal ideation. The study was performed in 4203 young adults (aged 18-35 years, 63.8% females). Data were collected using self-reports. Moderation analysis demonstrated that PLEs are associated with higher levels of the current suicidal ideation only in participants with greater severity of insomnia (B = 0.003, p < 0.001). This analysis included age, gender, education, occupation and depressive symptoms as covariates. Moreover, the network analysis demonstrated that nodes representing PLEs are connected to the node of current suicidal ideation only in participants with greater severity of insomnia. The nodes of PLEs connected to the current suicidal ideation node captured PLEs representing deja vu experiences, auditory hallucination-like experiences and paranoia (edge weights between 0.011 and 0.083). Furthermore, nodes representing PLEs were the three most central nodes in the network analysis of individuals with higher levels of insomnia (strength centrality between 0.96 and 1.10). In turn, the three most central nodes were represented by depressive symptoms in the network analysis of individuals with lower levels of insomnia (strength centrality between 0.67 and 0.79). Findings from this study indicate that insomnia might be an important risk factor of suicide in people with PLEs, especially those reporting deja vu experiences, auditory hallucination-like experiences and paranoia.

"Do not take that medication": negative prospective memory in Korsakoff's syndrome.

BACKGROUND: While prospective memory (i.e., the ability to execute a future plan) has been extensively researched, little is known about negative prospective memory (i.e., the ability to remember not to execute a future plan) in Korsakoff's syndrome (KS). We thus evaluated both prospective memory and negative prospective memory in KS, as well as the relationship between both types of prospective memory and inhibition. METHODS: Patients with KS and control participants were invited to press a button on the keyboard (i.e., prospective memory) or not to press a button when a cue word (e.g., negative prospective memory) was encountered. RESULTS: The analysis demonstrated that patients with KS had more prospective memory errors (i.e., forgetting to click the keyboard when the instruction was to do so) than control participants. The analysis also demonstrated that patients with KS had more negative prospective memory errors (i.e., clicking the keyboard when the instruction was not to do so) than control participants. Similar levels of commissions and omissions were observed in patients with KS than in control participants. Interestingly, prospective and negative prospective performances were significantly correlated with performance on an inhibition assessment task. DISCUSSION: Our study demonstrates that KS is characterized by not only difficulty in remembering to execute a future intention but also by difficulty in remembering not to execute a future intention. A decline in negative prospective memory in KS can be associated with difficulty in inhibiting no longer appropriate previously learned intentions.

The recombined memory: associative inference in Alzheimer's disease.

BACKGROUND: Associative inference refers to an adaptive ability that allows flexible recombination of information acquired during previous experiences to make new connections that they have not directly experienced. This cognitive ability has been widely associated with the hippocampus. AIMS: We investigated associative inference in patients with Alzheimer's disease and control participants. METHODS: The task has two phases. In the training phase, participants learned to encode overlapping pairs of objects (AB + BC). In the test phase, participants were invited to retrieve previously see associations (i.e., AB, BC) as well as novel associations between the previously exposed objects (i.e., AC). In addition, we test the relationship between associative inference and cognitive flexibility. RESULTS: Analysis demonstrated lower associative inference in AD patients than in control participants. Interestingly, performance on the associative inference task was significantly correlated with low performance on a cognitive flexibility task in AD patients. DISCUSSION: Our findings demonstrate a compromise of the ability to flexibly combine new representations from prior memories in AD, which is likely related to the hippocampal dysfunction in AD.

"Ten dollars today or 50 dollars after one month?" Temporal discounting in Korsakoff syndrome.

OBJECTIVE: Little research has investigated decision making in patients with Korsakoff syndrome (KS). Specifically, to our knowledge, there is a lack of research investigating whether patients with KS may tend to prefer immediate over future rewards (i.e., temporal discounting). Further, we investigated the relationship between temporal discounting and inhibition. METHODS: We, for the first time, invited patients with KS and control participants to perform a temporal discounting task, in which they answered questions probing preferences between an immediate, but smaller amount of money, and a delayed, but larger amount of money (e.g., "would you prefer 10 dollars today or 50 dollars after one month?"). Furthermore, inhibition was measured using the Stroop Colour Word Test. RESULTS: Analysis demonstrated higher temporal discounting in patients with KS than in control participants. Temporal discounting in both populations was significantly correlated with inhibition. CONCLUSIONS: Patients with KS may have difficulties to suppress the temptation of smaller, but immediate, rewards.

A novel treatment strategy to prevent Parkinson's disease: focus on iron regulatory protein 1 (IRP1).

We propose that neural damage in Parkinson's disease (PD) is due to dysregulation of iron utilization rather than to high iron levels per se. Iron deposits are associated with neuronal cell death in substantia nigra (SN) resulting in PD where high levels of iron in SNs are due to dysregulation of iron utilization. Cytosolic aconitase (ACO1) upon losing an iron-sulfur cluster becomes iron regulatory protein 1 (IRP1). Rotenone increases levels of IRP1 and induces PD in rats. An increase in iron leads to inactivation of IRP1. We propose a novel treatment strategy to prevent PD. Specifically in rats given rotenone by subcutaneous injections, iron, from iron carbonyl from which iron is slowly absorbed, given three times a day by gavage will keep iron levels constant in the gut whereby iron levels and iron utilization systematically can be tightly regulated. Rotenone adversely affects complex 1 iron-sulfur proteins. Iron supplementation will increase iron-sulfur cluster formation switching IRP1 to ACO1. With IRP1 levels kept constantly low, iron utilization will systematically be tightly regulated stopping dysregulation of complex 1 and the neural damage done by rotenone preventing PD.

The pupil and myself: pupil dilation during retrieval of self-defining memories.

BACKGROUND: There is a recent interest in pupil dilation during the retrieval of autobiographical memory. We pursued this line of research by measuring pupil diameter during the retrieval of self-defining memories, that is, memories that are highly vivid, emotionally intense, and are retrieved to reflect enduring concerns in a person's life. METHODS: We invited 40 participants to retrieve self-defining memories while their pupil activity was recorder with eye-tracking glasses. We analyzed memories regarding specificity (i.e., specific or general) and emotional valence (neutral, positive, negative, or mixed). RESULTS: Analysis demonstrated larger pupil diameter during the retrieval of specific than general self-defining memories. However, no significant differences in pupil diameter were observed across the four emotional categories of self-defining memories. DISCUSSION: The increased pupil size during retrieval of specific self-defining memories can be attributed to the autonoetic experience during retrieval of these memories and/or to the cognitive load as required to construct these memoires. By investigating pupil dilation during the retrieval of self-defining memories, our study provides an original, ecological, and reliable physiological assessment of these memories.

A systematic review of neural, cognitive, and clinical studies of anger and aggression.

Anger and aggression have large impact on people's safety and the society at large. In order to provide an intervention to minimise aggressive behaviours, it is important to understand the neural and cognitive aspects of anger and aggression. In this systematic review, we investigate the cognitive and neural aspects of anger-related processes, including anger-related behaviours and anger reduction. Using this information, we then review prior existing methods on the treatment of anger-related disorders as well as anger management, including mindfulness and cognitive behavioural therapy. At the cognitive level, our review that anger is associated with excessive attention to anger-related stimuli and impulsivity. At the neural level, anger is associated with abnormal functioning of the amygdala and ventromedial prefrontal cortex. In conclusions, based on cognitive and neural studies, we here argue that mindfulness based cognitive behavioural therapy may be better at reducing anger and aggression than other behavioural treatments, such as cognitive behavioural therapy or mindfulness alone. We provide key information on future research work and best ways to manage anger and reduce aggression. Importantly, future research should investigate how anger related behaviours is acquired and how stress impacts the development of anger.

Harnessing forgetfulness: can episodic-memory tests predict early Alzheimer's disease?

A rapid increase in the number of patients with Alzheimer's disease (AD) is expected over the next decades. Accordingly, there is a critical need for early-stage AD detection methods that can enable effective treatment strategies. In this study, we consider the ability of episodic-memory measures to predict mild cognitive impairment (MCI) to AD conversion and thus, detect early-stage AD. For our analysis, we studied 307 participants with MCI across four years using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Using a binary logistic regression, we compared episodic-memory tests to each other and to prominent neuroimaging methods in MCI converter (MCI participants who developed AD) and MCI non-converter groups (MCI participants who did not develop AD). We also combined variables to test the accuracy of mixed-predictor models. Our results indicated that the best predictors of MCI to AD conversion were the following: a combined episodic-memory and neuroimaging model in year one (59.8%), the Rey Auditory Verbal Learning Test in year two (71.7%), a mixed episodic-memory predictor model in year three (77.7%) and the Logical Memory Test in year four (77.2%) of ADNI. Overall, we found that individual episodic-memory measure and mixed models performed similarly when predicting MCI to AD conversion. Comparatively, individual neuroimaging measures predicted MCI conversion worse than chance. Accordingly, our results indicate that episodic-memory tests could be instrumental in detecting early-stage AD and enabling effective treatment.

Future-Oriented Repetitive Thought: Pessimistic View of Future in Patients With Alzheimer Disease.

OBJECTIVE: In this study, we, for the first time, evaluated future-oriented repetitive thought in patients with Alzheimer disease (AD), that is, how they think and worry about the future. METHODS: We administered the Future-Oriented Repetitive Thought scale to 34 patients with AD and 37 control participants. This scale assessed 3 categories of future-oriented repetitive thought: (1) pessimistic repetitive future thinking (eg, "I think about the possibility of losing people or things that are important to me"), (2) repetitive thinking about future goals (eg, "I make specific plans for how to get things that I want in life"), and (3) positive indulging about the future (eg, "When I picture good things happening in my future, it is as if they were actually happening to me now"). RESULTS: Analysis demonstrated more pessimistic repetitive future thinking, but less repetitive thinking about future goals and positive indulging about the future, in patients with AD than in control participants. CONCLUSION: Our findings demonstrate a pessimistic view of future in patients with AD, which is possibly attributed to hopelessness and depression.

Pupil dilation as an indicator of future thinking.

BACKGROUND: The pupil typically dilates in reaction to cognitive load. In this study, we, for the first time, investigated whether future thinking (i.e., the ability to generate hypothetical scenarios in the future) would result in pupil dilation. METHODS: We recorded pupil dilation of participants during two conditions: past and future thinking. In past thinking, we invited participants to retrieve past personal events, while in future thinking, we invited them to imagine an event that may occur in the future. RESULTS: Analysis demonstrated a larger pupil size during future than past thinking. Results also demonstrated longer retrieval time of future events compared with past ones, suggesting that future thinking perhaps requires more cognitive load than for past thinking. Interestingly, retrieval times during past and future thinking were positively correlated with pupil size. DISCUSSION: The finding that future thinking activates pupil dilation could be due to the fact that while both past and future thinking require retrieving information from memory, future, but not past, thinking additionally requires the ability to recombine this information into novel scenarios.

Human appetitive Pavlovian-to-instrumental transfer: a goal-directed account.

Pavlovian-to-instrumental transfer (PIT) tasks assess the impact of environmental stimuli on instrumental actions. Since their initial translation from animal to human experiments, PIT tasks have provided insight into the mechanisms that underlie reward-based behaviour. This review first examines the main types of PIT tasks used in humans. We then seek to contribute to the current debate as to whether human PIT effects reflect a controlled, goal-directed process, or a more automatic, non-goal-directed mechanism. We argue that the data favour a goal-directed process. The extent to which the major theories of PIT can account for these data is then explored. We discuss a number of associative accounts of PIT as well as dual-process versions of these theories. Ultimately, however, we favour a propositional account, in which human PIT effects are suggested to be driven by both perceived outcome availability and outcome value. In the final section of the review, we present the potential objections to the propositional approach that we anticipate from advocates of associative link theories and our response to them. We also identify areas for future research.

Methylphenidate improves executive functions in patients with traumatic brain injuries: a feasibility trial via the idiographic approach.

BACKGROUND: Road traffic accidents are known to be the main cause of traumatic brain injury (TBI). TBI is also a leading cause of death and disability. This study, by means of the idiographic approach (single-case experimental designs using multiple-baseline designs), has examined whether methylphenidate (MPH - trade name Ritalin) had a differential effect on cognitive measures among patients with TBI with the sequel of acute and chronic post-concussion syndromes. The effect on gender was also explored. METHODS: In comparison with healthy controls, patients with TBI (acute and chronic) and accompanying mild cognitive impairment (MCI) were screened for their integrity of executive functioning. Twenty-four patients exhibiting executive dysfunction (ED) were then instituted with the pharmacological intervention methylphenidate (MPH). The methylphenidate was administered using an uncontrolled, open label design. RESULTS: The administration of methylphenidate impacted ED in the TBI group but had no effect on mood. Attenuation of ED was more apparent in the chronic phases of TBI. The effect on gender was not statistically significant with regard to the observed changes. CONCLUSIONS: To our knowledge, this is the first feasibility trial from the Arabian Gulf to report the performance of a TBI population with mild cognitive impairment according to the IQCODE Arabic version. This investigation confirms anecdotal observations of methylphenidate having the potential to attenuate cognitive impairment; particularly those functions that are critically involved in the integrity of executive functioning. The present feasibility trial should be followed by nomothetic studies such as those that adhere to the protocol of the randomized controlled trial. This evidence-based research is the foundation for intervention and future resource allocation by policy- or public health decision-makers.

Evaluating the Sustained Attention Response Task to Quantify Cognitive Fluctuations in Dementia With Lewy Bodies.

Cognitive fluctuations (CFs) are a core diagnostic feature of dementia with Lewy bodies (DLB). Detection of CF is still mostly based on subjective reports from the patient or informant; more quantitative measures are likely to improve the accuracy for the diagnosis of DLB. The purpose of the current study is to test whether performance on the Sustained Attention Response Task (SART) could distinguish those patients with DLB with and without CF. Twenty-four patients with DLB were tested on the SART and performance was related to scores on the Clinical Assessment of Fluctuations (CAFs) and One Day Fluctuation Assessment Scale (ODFAS). The number of "misses" made was a significant predictor of their fluctuation severity, attentional performance, disorganized thinking, and language production ratings on the ODFAS. However, measures on the SART did not correlate with measures on the CAF scale. In conclusion, these findings suggest that SART is a feasible measure of sustained attention in this population and has clinical and diagnostic relevance to the measurement of CF, particularly those aspects measured by the ODFAS.

The subjective experience of mind wandering in Alzheimer's disease.

Introduction: Little is known about mind wandering in Alzheimer's disease (AD). In this study, we evaluated the subjective experience of mind wandering in AD.Methods: We invited AD patients and control participants to rate the occurrence, intentionality, emotionality, visual imagery, specificity, self-relatedness and temporal orientation of mind wandering.Results: Analysis showed that AD patients rated their mind wandering as more frequent, negative, and more oriented toward the past, but less vivid and specific than that of control participants. No significant differences were observed between AD patients and control participants regarding the intentionality or self-relatedness of mind wandering.Conclusions: These findings demonstrate the negative content in AD. Regarding the reduction of visual imagery and specificity during mind wandering, this reduction may mirror a diminished subjective experience of mind wandering in AD. Regarding temporality, our results may reflect a tendency of AD patients to reminisce over past experiences. Finally, mind wandering in AD seems to trigger significant self-related content.

Identifying the neural correlates of doorway freezing in Parkinson's disease.

Freezing of gait (FOG) in Parkinson's disease (PD) is frequently triggered upon passing through narrow spaces such as doorways. However, despite being common the neural mechanisms underlying this phenomenon are poorly understood. In our study, 19 patients who routinely experience FOG performed a previously validated virtual reality (VR) gait paradigm where they used foot-pedals to navigate a series of doorways. Patients underwent testing randomised between both their "ON" and "OFF" medication states. Task performance in conjunction with blood oxygenation level dependent (BOLD) signal changes between "ON" and "OFF" states were compared within each patient. Specifically, as they passed through a doorway in the VR environment patients demonstrated significantly longer "footstep" latencies in the OFF state compared to the ON state. As seen clinically in FOG this locomotive delay was primarily triggered by narrow doorways rather than wide doorways. Functional magnetic resonance imaging revealed that footstep prolongation on passing through doorways was associated with selective hypoactivation in the presupplementary motor area (pSMA) bilaterally. Task-based functional connectivity analyses revealed that increased latency in response to doorways was inversely correlated with the degree of functional connectivity between the pSMA and the subthalamic nucleus (STN) across both hemispheres. Furthermore, increased frequency of prolonged footstep latency was associated with increased connectivity between the bilateral STN. These findings suggest that the effect of environmental cues on triggering FOG reflects a degree of impaired processing within the pSMA and disrupted signalling between the pSMA and STN, thus implicating the "hyperdirect" pathway in the generation of this phenomenon.

Impaired Specificity of Future Thinking in Alcohol Use Disorders.

BACKGROUND: While there has been a body of work that has investigated past thinking in individuals with alcohol use disorders (AUD), little is known about future thinking in these individuals. METHODS: We invited participants with AUD and control participants to construct past and future events. We have also investigated the relationship between constructing past and future events and depression. RESULTS: By analyzing the specificity (i.e., the ability in constructing specific events situated in time and space) of these events, results demonstrated lower specificity of past and future thinking in AUD participants compared to control participants. No significant differences were observed between the specificity of past and future thinking in AUD or in control participants. Further, significant negative correlations were observed between depression and past/future thinking in AUD participants but not in controls. CONCLUSIONS: Difficulties in constructing specific future scenarios, as observed in AUD participants compared with controls, are presumably related to ruminative thinking and emotional avoidance aspects of depression, which should be investigated in future studies. More specifically, individuals with AUD may tend to construct general future scenarios to dwell on negative past events and/or to avoid coping with hopelessness and processing of upsetting or distressful future scenarios.

Visual imagery: The past and future as seen by patients with Alzheimer's disease.

We investigated visual imagery for past and future thinking in Alzheimer's Disease (AD). We invited AD patients and controls to retrieve past events and to imagine future events. Participants also provided a "Field" response if they see the event through their own eyes, or an "Observer" response if they see themselves in the scene as a spectator would. Less "Field" and more "Observer" responses were observed in AD participants than in controls during past and future thinking, suggesting a diminished ability to mentally visualize past and future events in AD. Results also demonstrated significant positive correlations between the production of "Field" responses and specificity during past and future thinking, suggesting a relationship between the ability to mentally visualize past and future events and autobiographical overgenerality in AD.

Future Thinking in Korsakoff Syndrome.

AIMS: Prior research has been mainly concerned with the ability of patients with Korsakoff syndrome (KS) to project themselves into the past. Little is known about the patients' ability to project themselves into the future. We therefore compared past and future thinking in patients with KS. METHODS: We invited patients with KS and control participants to retrieve past events and reconstruct future events. Participants were also invited to rate subjective characteristics (i.e. time travel, emotional feeling, and visual imagery) of the past and future events. RESULTS: Patients with KS demonstrated low specificity, time travel, and emotional experience during past and future thinking. However, while lower emotional experience was observed in patients with KS than in the control participants during future thinking, no significant differences were observed between the two populations during past thinking. Regarding within-group comparisons, patients with KS demonstrated no significant differences between past and future thinking in terms of specificity, time travel, and visual imagery; however, they demonstrated higher emotional experience during past than during future thinking. Regarding control participants, they demonstrated no significant differences between past and future thinking in terms of specificity, time travel, emotional experience, and visual imagery. CONCLUSION: Our findings demonstrate a diminished ability to construct specific future scenarios as well as a diminished subjective experience during future thinking in KS.