Shifting from the perceptual brain to the logical brain: the neural impact of cognitive inhibition training

What happens in the human brain when the mind has to inhibit a perceptual process in order to activate a logical reasoning process? Here, we use functional imaging to show the networks of brain areas involved in a deductive logic task performed twice by the same subjects, first with a perceptual bias and then with a logical response following bias-inhibition training. The main finding is a striking shift in the cortical anatomy of reasoning from the posterior part of the brain (the ventral and dorsal pathways) to a left-prefrontal network including the middle-frontal gyrus, Broca's area, the anterior insula, and the pre-SMA. This result indicates that such brain shifting is an essential element for human access to logical thinking.     

Logic as a tool for clinical training in social work

The paper is an attempt to illustrate the usefulness of logic as a technique in the clinical training of mental health professionals. The specific concepts that are examined include the nature of deductive and inductive reasoning, hypothesis testing, necessary and sufficient conditions, if-then propositions, and the nature of clinical evidence. Knowledge and use of these concepts was tested in a tutorial program directed toward students who were beginning graduate studies in the field of social work. Some of the difficulties encountered by these students, especially in the clinical aspects of their training, were directly related to an inadequate understanding of these logical forms of reasoning. It is suggested that a portion of the clinical training in mental health fields be directed towards a deeper understanding and utilization of these basic concepts.     

Neuropsychiatric subsyndromes and brain metabolic network dysfunctions in early onset Alzheimer's disease

Neuropsychiatric symptoms (NPSs) often occur in early‐age‐of‐onset Alzheimer's disease (EOAD) and cluster into sub‐syndromes (SSy). The aim of this study was to investigate the association between ¹⁸F‐FDG‐PET regional and connectivity‐based brain metabolic dysfunctions and neuropsychiatric SSy. NPSs were assessed in 27 EOAD using the Neuropsychiatric Inventory and further clustered into four SSy (apathetic, hyperactivity, affective, and psychotic SSy). Eighty‐five percent of EOAD showed at least one NPS. Voxel‐wise correlations between SSy scores and brain glucose metabolism (assessed with ¹⁸F‐FDG positron emission tomography) were studied. Interregional correlation analysis was used to explore metabolic connectivity in the salience (aSN) and default mode networks (DMN) in a larger sample of EOAD (N = 51) and Healthy Controls (N = 57). The apathetic, hyperactivity, and affective SSy were highly prevalent (>60%) as compared to the psychotic SSy (33%). The hyperactivity SSy scores were associated with increase of glucose metabolism in frontal and limbic structures, implicated in behavioral control. A comparable positive correlation with part of the same network was found for the affective SSy scores. On the other hand, the apathetic SSy scores were negatively correlated with metabolism in the bilateral orbitofrontal and dorsolateral frontal cortex known to be involved in motivation and decision‐making processes. Consistent with these SSy regional correlations with brain metabolic dysfunction, the connectivity analysis showed increases in the aSN and decreases in the DMN. Behavioral abnormalities in EOAD are associated with specific dysfunctional changes in brain metabolic activity, in particular in the aSN that seems to play a crucial role in NPSs in EOAD. Hum Brain Mapp 37:4234–4247, 2016. © 2016 Wiley Periodicals, Inc.     

A model of neurological disorder: a basis for logical and structured thinking and reasoning in neurology

A model of neurological disorder in graphical form, based upon a model proposed by the World Health Organisation, is presented. This model is intended to be a basis for a logical and structured thinking and reasoning in neurology, not least in diagnosis. The model is a chain of basic elements in which each element causes the following one. The chain can be divided in two parts. The first part is: Etiology → Pathology → Manifestation. Pathology is described by the properties of the lesion in the nervous system. Manifestation is the symptoms and signs, that can be summarised as Semiology, in fact, synonymous with Impairment. The second part of the model is then: Manifestation (= Impairment) → Disability → Handicap. The terms disease and disorder are not contained within the chain of basic elements. The manifestation gives the patient an awareness of disorder and the condition may be classified as syndrome or disease. Neither the awareness of disorder nor the classification influences the chain of basic elements.     

A failure of conflict to modulate dual-stream processing may underlie the formation and maintenance of delusions

BackgroundDual-stream information processing proposes that reasoning is composed of two interacting processes: a fast, intuitive system (Stream 1) and a slower, more logical process (Stream 2). In non-patient controls, divergence of these streams may result in the experience of conflict, modulating decision-making towards Stream 2, and initiating a more thorough examination of the available evidence. In delusional schizophrenia patients, a failure of conflict to modulate decision-making towards Stream 2 may reduce the influence of contradictory evidence, resulting in a failure to correct erroneous beliefs.MethodDelusional schizophrenia patients and non-patient controls completed a deductive reasoning task requiring logical validity judgments of two-part conditional statements. Half of the statements were characterized by a conflict between logical validity (Stream 2) and content believability (Stream 1).ResultsPatients were significantly worse than controls in determining the logical validity of both conflict and non-conflict conditional statements. This between groups difference was significantly greater for the conflict condition.ConclusionsThe results are consistent with the hypothesis that delusional schizophrenia patients fail to use conflict to modulate towards Stream 2 when the two streams of reasoning arrive at incompatible judgments. This finding provides encouraging preliminary support for the Dual-Stream Modulation Failure model of delusion formation and maintenance.     

Hemodynamic response function abnormalities in schizophrenia during a multisensory detection task

Functional magnetic resonance imaging (fMRI) of the blood oxygen level dependent (BOLD) response has commonly been used to investigate the neuropathology underlying cognitive and sensory deficits in patients with schizophrenia (SP) by examining the positive phase of the BOLD response, assuming a fixed shape for the hemodynamic response function (HRF). However, the individual phases (positive and post‐stimulus undershoot (PSU)) of the HRF may be differentially affected by a variety of underlying pathologies. The current experiment used a multisensory detection task with a rapid event‐related fMRI paradigm to investigate both the positive and PSU phases of the HRF in SP and healthy controls (HC). Behavioral results indicated no significant group differences during task performance. Analyses that examined the shape of the HRF indicated two distinct group differences. First, SP exhibited a reduced and/or prolonged PSU following normal task‐related positive BOLD activation in secondary auditory and visual sensory areas relative to HC. Second, SP did not show task‐induced deactivation in the anterior node of the default‐mode network (aDMN) relative to HC. In contrast, when performing traditional analyses that focus on the positive phase, there were no group differences. Interestingly, the magnitude of the PSU in secondary auditory and visual areas was positively associated with the magnitude of task‐induced deactivation within the aDMN, suggesting a possible common neural mechanism underlying both of these abnormalities (failure in neural inhibition). Results are consistent with recent views that separate neural processes underlie the two phases of the HRF and that they are differentially affected in SP. Hum Brain Mapp 37:745–755, 2016. © 2015 Wiley Periodicals, Inc.     

At the core of reasoning: Dissociating deductive and non‐deductive load

In recent years, neuroimaging methods have been used to investigate how the human mind carries out deductive reasoning. According to some, the neural substrate of language is integral to deductive reasoning. According to others, deductive reasoning is supported by a language‐independent distributed network including left frontopolar and frontomedial cortices. However, it has been suggested that activity in these frontal regions might instead reflect non‐deductive factors such as working memory load and general cognitive difficulty. To address this issue, 20 healthy volunteers participated in an fMRI experiment in which they evaluated matched simple and complex deductive and non‐deductive arguments in a 2 × 2 design. The contrast of complex versus simple deductive trials resulted in a pattern of activation closely matching previous work, including frontopolar and frontomedial “core” areas of deduction as well as other “cognitive support” areas in frontoparietal cortices. Conversely, the contrast of complex and simple non‐deductive trials resulted in a pattern of activation that does not include any of the aforementioned “core” areas. Direct comparison of the load effect across deductive and non‐deductive trials further supports the view that activity in the regions previously interpreted as “core” to deductive reasoning cannot merely reflect non‐deductive load, but instead might reflect processes specific to the deductive calculus. Finally, consistent with previous reports, the classical language areas in left inferior frontal gyrus and posterior temporal cortex do not appear to participate in deductive inference beyond their role in encoding stimuli presented in linguistic format.     

Diagnostic reasoning in neurology. An analysis of the more frequent errors

Diagnostic reasoning is a cognitive proccess that has various performance and results. There are several kinds of clinical reasoning, such as model or pattern recognizing, causal or physiopathologic reasoning, deterministic, exhaustive, and hypotetic-deductive ones. Each form of reasoning may be relevant in certain clinical context, and all of the forms are also complementary. The logical consequence of diagnostic reasoning, like every cognitive proccess, is a clinical error. It is necessary that the neurologist knows the principles of diagnostic reasoning and the more frequent errors and biases. These can be summarized as: errors associated with the proccess of taking history and clinical examination, mnesic and semantic components of clinical reasoning, failure of hipotetic- deductive reasoning, and inadequate use of probability theory in Medicine.     

Ubiquitin proteasome system in Parkinson's disease: A keeper or a witness?

ObjectiveThe aim of this work was to evaluate the role of ubiquitin–proteasome system (UPS) on mitochondrial-driven alpha-synuclein (aSN) clearance in in vitro, ex vivo and in vivo Parkinson's disease (PD) cellular models.MethodWe used SH-SY5Y ndufa2 knock-down (KD) cells, PD cybrids and peripheral blood mononuclear cells (PBMC) from patients meeting the diagnostic criteria for PD. We quantified aSN aggregation, proteasome activity and protein ubiquitination levels. In PBMC of PD patient population we evaluated the aSN levels in the plasma and the influence of several demographic characteristics in the above mentioned determinations.ResultsWe found that ubiquitin-independent proteasome activity was up-regulated in SH-SY5Y ndufa2 KD cells while a downregulation was observed in PD cybrids and PBMC. Moreover, we observed an increase in protein ubiquitination that correlates with a decrease in ubiquitin-dependent proteasome activity. Accordingly, proteasome inhibition prevented ubiquitin-dependent aSN clearance. Ubiquitin-independent proteasome activity was positively correlated with ubiquitination in PBMC.We also report a negative correlation of chymotrypsin-like activity with age in control and late-onset PD groups. Total ubiquitin content is positively correlated with aSN oligomer levels, which leads to an age-dependent increase of aSN ubiquitination in LOPD. Moreover, aSN levels are increased in the plasma of PD patients.InterpretationaSN oligomers are ubiquitinated and we identified a ubiquitin-dependent clearance insufficiency with the accumulation of both aSN and ubiquitin. However, SH-SY5Y ndufa2 KD cells showed a significant up-regulation of ubiquitin-independent proteasomal enzymatic activity that could mean a cell rescue attempt. Moreover, we identified that UPS function is age-dependent in PBMC.     

Metastable neural dynamics underlies cognitive performance across multiple behavioural paradigms

Despite resting state networks being associated with a variety of cognitive abilities, it remains unclear how these local areas act in concert to express particular cognitive operations. Theoretical and empirical accounts indicate that large‐scale resting state networks reconcile dual tendencies towards integration and segregation by operating in a metastable regime of their coordination dynamics. Metastability may confer important behavioural qualities by binding distributed local areas into large‐scale neurocognitive networks. We tested this hypothesis by analysing fMRI data in a large cohort of healthy individuals (N = 566) and comparing the metastability of the brain's large‐scale resting network architecture at rest and during the performance of several tasks. Metastability was estimated using a well‐defined collective variable capturing the level of 'phase‐locking' between large‐scale networks over time. Task‐based reasoning was principally characterised by high metastability in cognitive control networks and low metastability in sensory processing areas. Although metastability between resting state networks increased during task performance, cognitive ability was more closely linked to spontaneous activity. High metastability in the intrinsic connectivity of cognitive control networks was linked to novel problem solving or fluid intelligence, but was less important in tasks relying on previous experience or crystallised intelligence. Crucially, subjects with resting architectures similar or 'pre‐configured' to a task‐general arrangement demonstrated superior cognitive performance. Taken together, our findings support a key linkage between the spontaneous metastability of large‐scale networks in the cerebral cortex and cognition.     

The dynamics of deductive reasoning: an fMRI investigation

Although the basis for deductive reasoning has been a traditional focus of philosophical discussion, the neural correlates and mechanisms that underlie deductive reasoning have only recently become the focus of scientific investigation. In syllogistic deductive reasoning information presented in two related sequential premises leads to a subsequent conclusion. While previous imaging studies have identified frontal, parietal, temporal, and occipital complexes that are activated during these reasoning events, there are substantive differences among the findings with respect to the specific regions engaged in reasoning and the contribution of language areas. Further, little is known about the various stages of information processing during reasoning. Using event-related fMRI and an auditory and visual conjunction technique, we identified a long-range supramodal network active during reasoning processes including areas in the left frontal and parietal regions as well as the bilateral caudate nucleus. Time courses of activation for each of these regions suggest that reasoning processes emerge during the presentation of the second premise, and remain active until the validation of the conclusion. Thus, areas within the frontal and parietal regions are differentially engaged at different time points in the reasoning process consistent with coordinated intra-network interactions.     

Common and distinct brain networks underlying verbal and visual creativity

Creativity is imperative to the progression of human civilization, prosperity, and well‐being. Past creative researches tends to emphasize the default mode network (DMN) or the frontoparietal network (FPN) somewhat exclusively. However, little is known about how these networks interact to contribute to creativity and whether common or distinct brain networks are responsible for visual and verbal creativity. Here, we use functional connectivity analysis of resting‐state functional magnetic resonance imaging data to investigate visual and verbal creativity‐related regions and networks in 282 healthy subjects. We found that functional connectivity within the bilateral superior parietal cortex of the FPN was negatively associated with visual and verbal creativity. The strength of connectivity between the DMN and FPN was positively related to both creative domains. Visual creativity was negatively correlated with functional connectivity within the precuneus of the pDMN and right middle frontal gyrus of the FPN, and verbal creativity was negatively correlated with functional connectivity within the medial prefrontal cortex of the aDMN. Critically, the FPN mediated the relationship between the aDMN and verbal creativity, and it also mediated the relationship between the pDMN and visual creativity. Taken together, decreased within‐network connectivity of the FPN and DMN may allow for flexible between‐network coupling in the highly creative brain. These findings provide indirect evidence for the cooperative role of the default and executive control networks in creativity, extending past research by revealing common and distinct brain systems underlying verbal and visual creative cognition. Hum Brain Mapp 38:2094–2111, 2017. © 2017 Wiley Periodicals, Inc.     

Polarity-specific high-definition transcranial direct current stimulation of the anterior and posterior default mode network improves remote memory retrieval

BackgroundPrevious studies show that activity in the posterior default mode network (pDMN), including the posterior cingulate cortex and the precuneus, is correlated with the success of long-term episodic memory retrieval. However, the role of the anterior DMN (aDMN) including the medial prefrontal cortex is still unclear. Some studies show that activating the medial prefrontal cortex improves memory retrieval while other studies show deactivation of the medial prefrontal cortex in successful retrieval of episodic memories, suggesting a possible functional dissociation between the aDMN and pDMN.ObjectiveIn the current study, we aim to causally explore this probable dissociation using high-definition transcranial direct current stimulation (HD-tDCS).MethodsWe perform a randomised double-blinded two-visit placebo-controlled study with 84 healthy young adults. During Visit 1 they learn 75 Swahili-English word-associations. Seven days later, they randomly receive either anodal, cathodal or sham HD-tDCS targeting the pDMN or aDMN while they recall what they have previously learned.ResultsWe demonstrate that anodal stimulation of the pDMN and cathodal stimulation of the aDMN, equally improve the percentage of Swahili-English word-associations recalled 7 days after learning.ConclusionsModulating the activity in the aDMN and pDMN causally affect memory retrieval performance. HD-tDCS of the aDMN and pDMN shows that anodal stimulation of the pDMN and cathodal stimulation of the aDMN increases memory retrieval performance one week after the learning phase. Given consistent evidence, it is highly likely that we are increasing the activity in the pDMN with anodal pDMN stimulation. However, it is not clear if cathodal HD-tDCS targetting aDMN works via decoupling from the pDMN or via indirectly disinhibit pDMN.     

Distributed neural representations of logical arguments in school‐age children

Children's understanding of linear‐order (e.g., Dan is taller than Lisa, Lisa is taller than Jess) and set‐inclusion (i.e., All tulips are flowers, All flowers are plants) relationships is critical for the acquisition of deductive reasoning, that is, the ability to reach logically valid conclusions from given premises. Behavioral and neuroimaging studies in adults suggest processing differences between these relations: While arguments that involve linear‐orders may be preferentially associated with spatial processing, arguments that involve set‐inclusions may be preferentially associated with verbal processing. In this study, we used functional magnetic resonance imaging to investigate whether these processing differences appear during the period of elementary school in development. Consistent with previous studies in adults, we found that arguments that involve linear‐order and set‐inclusion relationships preferentially involve spatial and verbal brain mechanisms (respectively) in school‐age children (9–14 year olds). Because this neural sensitivity was not related to age, it likely emerges before the period of elementary education. However, the period of elementary education might play an important role in shaping the neural processing of logical reasoning, as indicated by developmental changes in frontal and parietal regions that were dependent on the type of relation. Hum Brain Mapp 36:996–1009, 2015. © 2014 Wiley Periodicals, Inc.     

Attentional reorientation along the meridians of the visual field: Are there different neural mechanisms at play?

Hemispatial neglect, after unilateral lesions to parietal brain areas, is characterized by an inability to respond to unexpected stimuli in contralesional space. As the visual field's horizontal meridian is most severely affected, the brain networks controlling visuospatial processes might be tuned explicitly to this axis. We investigated such a potential directional tuning in the dorsal and ventral frontoparietal attention networks, with a particular focus on attentional reorientation. We used an orientation‐discrimination task where a spatial precue indicated the target position with 80% validity. Healthy participants (n = 29) performed this task in two runs and were required to (re‐)orient attention either only along the horizontal or the vertical meridian, while fMRI and behavioral measures were recorded. By using a general linear model for behavioral and fMRI data, dynamic causal modeling for effective connectivity, and other predictive approaches, we found strong statistical evidence for a reorientation effect for horizontal and vertical runs. However, neither neural nor behavioral measures differed between vertical and horizontal reorienting. Moreover, models from one run successfully predicted the cueing condition in the respective other run. Our results suggest that activations in the dorsal and ventral attention networks represent higher‐order cognitive processes related to spatial attentional (re‐)orientating that are independent of directional tuning and that unilateral attention deficits after brain damage are based on disrupted interactions between higher‐level attention networks and sensory areas.     

Spatial imagery in deductive reasoning: a functional MRI study

Various cognitive theories aim to explain human deductive reasoning: (1) mental logic theories claim syntactic language-based proofs of derivation, (2) the mental model theory proposes cognitive processes of constructing and manipulating spatially organized mental models, and (3) imagery theories postulate that such abilities are based on visual mental images. To explore the neural substrates of human deductive reasoning, we examined BOLD (blood oxygen level dependent) contrasts of twelve healthy participants during relational and conditional reasoning with whole-brain functional magnetic resonance imaging (fMRI). The results indicate that, in the absence of any correlated visual input, reasoning activated an occipitoparietal-frontal network, including parts of the prefrontal cortex (Brodmann's area, BA, 6, 9) and the cingulate gyrus (BA 32), the superior and inferior parietal cortex (BA 7, 40), the precuneus (BA 7), and the visual association cortex (BA 19). In the discussion, we first focus on the activated occipito-parietal pathway that is well known to be involved in spatial perception and spatial working memory. Second, we briefly relate the activation in the prefrontal cortical areas and in the anterior cingulate gyrus to other imaging studies on higher cognitive functions. Finally, we draw some general conclusions and argue that reasoners envisage and inspect spatially organized mental models to solve deductive inference problems.     

Resting‐state and task‐based centrality of dorsolateral prefrontal cortex predict resilience to 1 Hz repetitive transcranial magnetic stimulation

Repetitive transcranial magnetic stimulation (rTMS) is used to investigate normal brain function in healthy participants and as a treatment for brain disorders. Various subject factors can influence individual response to rTMS, including brain network properties. A previous study by our group showed that “virtually lesioning” the left dorsolateral prefrontal cortex (dlPFC; important for cognitive flexibility) using 1 Hz rTMS reduced performance on a set‐shifting task. We aimed to determine whether this behavioural response was related to topological features of pre‐TMS resting‐state and task‐based functional networks. 1 Hz (inhibitory) rTMS was applied to the left dlPFC in 16 healthy participants, and to the vertex in 17 participants as a control condition. Participants performed a set‐shifting task during fMRI at baseline and directly after a single rTMS session 1–2 weeks later. Functional network topology measures were calculated from resting‐state and task‐based fMRI scans using graph theoretical analysis. The dlPFC‐stimulated group, but not the vertex group, showed reduced setshifting performance after rTMS, associated with lower task‐based betweenness centrality (BC) of the dlPFC at baseline (p = .030) and a smaller reduction in task‐based BC after rTMS (p = .024). Reduced repeat trial accuracy after rTMS was associated with higher baseline resting state node strength of the dlPFC (p = .017). Our results suggest that behavioural response to 1 Hz rTMS to the dlPFC is dependent on baseline functional network features. Individuals with more globally integrated stimulated regions show greater resilience to rTMS effects, while individuals with more locally well‐connected regions show greater vulnerability.     

Causal interactions in attention networks predict behavioral performance

Lesion and functional brain imaging studies have suggested that there are two anatomically nonoverlapping attention networks. The dorsal frontoparietal network controls goal-oriented top-down deployment of attention; the ventral frontoparietal network mediates stimulus-driven bottom-up attentional reorienting. The interaction between the two networks and its functional significance has been considered in the past but no direct test has been carried out. We addressed this problem by recording fMRI data from human subjects performing a trial-by-trial cued visual spatial attention task in which the subject had to respond to target stimuli in the attended hemifield and ignore all stimuli in the unattended hemifield. Correlating Granger causal influences between regions of interest with behavioral performance, we report two main results. First, stronger Granger causal influences from the dorsal attention network (DAN) to the ventral attention network (VAN), i.e., DAN→VAN, are generally associated with enhanced performance, with right intraparietal sulcus (IPS), left IPS, and right frontal eye field being the main sources of behavior-enhancing influences. Second, stronger Granger causal influences from VAN to DAN, i.e., VAN→DAN, are generally associated with degraded performance, with right temporal-parietal junction being the main sources of behavior-degrading influences. These results support the hypothesis that signals from DAN to VAN suppress and filter out unimportant distracter information, whereas signals from VAN to DAN break the attentional set maintained by the dorsal attention network to enable attentional reorienting.