Timothy Joseph Lane

Most mental disorders affect only a small segment of the population. On the reasonable assumption that minds or brains are prone to occasional malfunction, these disorders do not seem to pose distinctive explanatory problems. Depression, however, because it is so prevalent and costly, poses a conundrum that some try to explain by characterizing it as an adaptation—a trait that exists because it performed fitness-enhancing functions in ancestral populations. Heretofore, proposed evolutionary explanations of depression did not focus on thought processes; instead, they emphasized that it facilitates navigation of adverse social circumstances or promotes immune response to infectious agents. According to a new hypothesis, the “analytical rumination hypothesis” (ARH), however, depression’s crucial adaptive trait is rumination—negative, intrusive thought. ARH holds that, (i) social dilemmas trigger depressed mood; (ii) depressed mood induces changes in body systems that facilitate ruminative analysis aimed at solving dilemmas; and, (iii) depressive rumination is a fitness-enhancing trait that was selected for in evolutionary time. Jointly, (i)~(iii) imply that we should not think of rumination as a disorder; instead, it is a trade-off, an eminently rational one. In the same way that fever solves a problem—coordination of the immune system in response to infection—so too does depressive rumination solve a problem, a social dilemma, albeit at the cost of inducing anhedonia and other maladies. But they argue that the cost is worthwhile, something that should be endured “until the problem is solved.” First, we argue that there are two distinct types of rumination, brooding and pondering; the former is associated with a disposition for depression, not the latter. But only the latter has the problem-solving capabilities that ARH requires. Second, recent brain imaging studies of depression reveal resting state hypoactivity in lateral regions and hyperactivity in paralimbic regions; this asymmetric pattern correlates with heightened levels of brooding, self-focused rumination. In other words, on the personal level, patients are trapped within self, isolated from the external world and suffused with negative affect; on the subpersonal level, this pattern is reflected by an asymmetric pattern of lateral vs. paralimbic resting state activity. Third, we proceed to conjecture that rational responses (e.g., pondering) to social dilemmas are those that strike a balance between internal and external considerations in the process of belief formation. Fourth, because the asymmetric resting state activity blocks those who suffer with depression from accessing and processing potentially positive stimuli from the external world, the capacity for rational, analytic response—hence, problem-solving—is constrained. Fifth, it follows that, although there might be conditions for which suffering should be endured rather than pharmacologically alleviated, depression is not one of those. Indeed, in view of the effects of the asymmetric resting state pattern, it is unlikely that depressive rumination would have been useful even for ancestral populations.

Nonrapid eye movement (NREM) sleep is associated with fading consciousness in humans. Recent neuroimaging studies have demonstrated the spatiotemporal alterations of the brain functional connectivity (FC) in NREM sleep, suggesting the changes of information integration in the sleeping brain. However, the common stationarity assumption in FC does not satisfactorily explain the dynamic process of information integration during sleep. The dynamic FC (dFC) across brain networks is speculated to better reflect the time-varying information propagation during sleep. Accordingly, we conducted simultaneous EEG-fMRI recordings involving 12 healthy men during sleep and observed dFC across sleep stages using the sliding-window approach. We divided dFC into two aspects: mean dFC (dFCmean) and variance dFC (dFCvar). A high dFCmean indicates stable brain network integrity, whereas a high dFCvar indicates instability of information transfer within and between functional networks. For the network-based dFC, the dFCvar were negatively correlated with the dFCmean across the waking and three NREM sleep stages. As sleep deepened, the dFCmean decreased (N0~N1 > N2 > N3), whereas the dFCvar peaked during the N2 stage (N0~N1 < N3 < N2). The highest dFCvar during the N2 stage indicated the unstable synchronizations across the entire brain. In the N3 stage, the overall disrupted network integration was observed through the lowest dFCmean and elevated dFCvar, compared with N0 and N1. Conclusively, when the network specificity (dFCmean) breaks down, the consciousness dissipates with increasing variability of information exchange (dFCvar).

Objective: Alterations in psychomotor dimension cut across different psychiatric disorders, such as schizophrenia (SCZ) and bipolar disorder (BD). This preliminary study aimed to investigate the organization of intrinsic brain activity in the subcortical-cortical sensorimotor system in SCZ (and BD) as characterized according to psychomotor dimension. Method: In this resting-state functional magnetic resonance imaging (fMRI) study, functional connectivity (FC) between thalamus and sensorimotor network (SMN), along with FC from substantia nigra (SN) and raphe nuclei (RN) to basal ganglia (BG) and thalamic regions, were investigated by using an a-priori-driven and dimensional approach. This was done in two datasets: SCZ patients showing inhibited psychomotricity (n = 18) vs. controls (n = 19); SCZ patients showing excited psychomotricity (n = 20) vs. controls (n = 108). Data from a third dataset of BD in inhibited depressive or manic phases (reflecting inhibited or excited psychomotricity) were used as control. Results: SCZ patients suffering from psychomotor inhibition showed decreased thalamus-SMN FC toward around-zero values paralleled by a concomitant reduction of SN-BG/thalamus FC and RN-BG/thalamus FC (as BD patients in inhibited depression). By contrast, SCZ patients suffering from psychomotor excitation exhibited increased thalamus-SMN FC toward positive values paralleled by a concomitant reduction of RN-BG/thalamus FC (as BD patients in mania). Conclusions: These findings suggest that patients exhibiting low or high levels of psychomotor activity show distinct patterns of thalamus-SMN coupling, which could be traced to specific deficit in SN- or RN-related connectivity. Notably, this was independent from the diagnosis of SCZ or BD, supporting an RDoC-like dimensional approach to psychomotricity.

Susceptibility to the rubber hand illusion (RHI) varies. To date, however, there is no consensus explanation of this variability. Previous studies, focused on the role of multisensory integration, have searched for neural correlates of the illusion. But those studies have failed to identify a sufficient set of functionally specific neural correlates. Because some evidence suggests that frontal α power is one means of tracking neural instantiations of self, we hypothesized that the higher the frontal α power during the eyes-closed resting state, the more stable the self. As a corollary, we infer that the more stable the self, the less susceptible are participants to a blurring of boundaries—to feeling that the rubber hand belongs to them. Indeed, we found that frontal α amplitude oscillations negatively correlate with susceptibility. Moreover, since lower frequencies often modulate higher frequencies, we explored the possibility that this might be the case for the RHI. Indeed, some evidence suggests that high frontal α power observed in low-RHI participants is modulated by δ frequency oscillations. We conclude that while neural correlates of multisensory integration might be necessary for the RHI, sufficient explanation involves variable intrinsic neural activity that modulates how the brain responds to incompatible sensory stimuli.

Neural activity varies continually from moment to moment. Such temporal variability (TV) has been highlighted as a functionally specific brain property playing a fundamental role in cognition. We sought to investigate the mechanisms involved in TV changes between two basic behavioral states, namely having the eyes open (EO) or eyes closed (EC) in vivo in humans. To these ends we acquired BOLD fMRI, ASL, and [18F]-fluoro-deoxyglucose PET in a group of healthy participants (n = 15), along with BOLD fMRI and [18F]-flumazenil PET in a separate group (n = 19). Focusing on an EO- vs EC-sensitive region in the occipital cortex (identified in an independent sample), we show that TV is constrained in the EO condition compared to EC. This reduction is correlated with an increase in energy consumption and with regional GABAA receptor density. This suggests that the modulation of TV by behavioral state involves an increase in overall neural activity that is related to an increased effect from GABAergic inhibition in addition to any excitatory changes. These findings contribute to our understanding of the mechanisms underlying activity variability in the human brain and its control.

Cerebrospinal fluid (CSF) is a fluidic part of the brain’s microenvironment that isolates the brain from the rest of the body. CSF dilutes metabolites from neuronal activities and removes them from the brain. Its production and resorption are regulated dynamically and are central to maintaining brain homeostasis. We discovered that the major CSF source, the choroid plexus (CP), harbors the brain’s strongest circadian clock. Here, we consider some implications of the CP circadian clock for metabolite clearance in the brain. If the circadian clock contributes to timed production of the CSF, its synchronization with sleep timing can maximize clearance efficiency and help prevent neurodegenerative diseases such as Alzheimer’s disease.

Neurovascular coupling (NVC), the transient regional hyperemia following the evoked neuronal responses, is the basis of blood oxygenation level-dependent techniques and is generally adopted across physiological conditions, including the intrinsic resting state. However, the possibility of neurovascular dissociations across physiological alterations is indicated in the literature. To examine the NVC stability across sleep–wake states, we used electroencephalography (EEG) as the index of neural activity and functional magnetic resonance imaging (fMRI) as the measure of cerebrovascular response. Eight healthy adults were recruited for simultaneous EEG-fMRI recordings in nocturnal sleep. We compared the cross-modality (EEG vs. fMRI) consistency of functional indices (spectral amplitude and functional connectivity) among five states of wakefulness and sleep (state effect). We also segregated the brain into three main partitions (anterior, middle and posterior) for spatial assessments (regional effect). Significant state effects were found on δ, α and fMRI indices and regional effects on the α and fMRI indices. However, the cross-state EEG changes in spectral amplitude and functional connectivity did not consistently match the changes in the fMRI indices across sleep–wake states. In spectral amplitude, the δ band peaked at the N3 stage for all brain regions, while the fMRI fluctuation amplitude peaked at the N2 stage in the central and posterior regions. In regional connectivity, the inter-hemispheric connectivity of the δ band peaked at the N3 stage for all regions, but the bilateral fMRI connectivity showed the state changes in the anterior and central regions. The cross-modality inconsistencies across sleep–wake states provided preliminary evidence that the neurovascular relationship may not change in a linear consistency during NREM sleep. Thus, caution shall be exercised when applying the NVC presumption to investigating sleep/wake transitions, even among healthy young adults.

Patient suffering of major depressive disorder (MDD) often complain that subjective time seems to “drag” with respect to physical time. This may point toward a generalized dysfunction of temporal processing in MDD. In the present study, we investigated temporal preparation in MDD. “Temporal preparation” refers to an increased readiness to act before an expected event; consequently, reaction time should be reduced. MDD patients and age-matched controls were required to make a saccadic eye movement between a central and an eccentric visual target after a variable duration preparatory period. We found that MDD patients produced a larger number of premature saccades, saccades initiated prior to the appearance of the expected stimulus. These saccades were not temporally controlled; instead, they seemed to reflect reduced inhibitory control causing oculomotor impulsivity. In contrast, the latency of visually guided saccades was strongly influenced by temporal preparation in controls; significantly less so, in MDD patients. This observed reduced temporal preparation in MDD was associated with a faster decay of short-term temporal memory. Moreover, in patients producing a lot of premature responses, temporal preparation to early imperative stimuli was increased. In conclusion, reduced temporal preparation and short-term temporal memory in the oculomotor domain supports the hypothesis that temporal processing was altered in MDD patients. Moreover, oculomotor impulsivity interacted with temporal preparation. These observed deficits could reflect other underlying aspects of abnormal time experience in MDD.

Objective Manic and depressive phases of bipolar disorder (BD) show opposite psychomotor symptoms. Neuronally, these may depend on altered relationships between sensorimotor network (SMN) and subcortical structures. The study aimed to investigate the functional relationships of SMN with substantia nigra (SN) and raphe nuclei (RN) via subcortical-cortical loops, and their alteration in bipolar mania and depression, as characterized by psychomotor excitation and inhibition. Method In this resting-state functional magnetic resonance imaging (fMRI) study on healthy (n = 67) and BD patients (n = 100), (1) functional connectivity (FC) between thalamus and SMN was calculated and correlated with FC from SN or RN to basal ganglia (BG)/thalamus in healthy; (2) using an a-priori-driven approach, thalamus-SMN FC, SN-BG/thalamus FC, and RN-BG/thalamus FC were compared between healthy and BD, focusing on manic (n = 34) and inhibited depressed (n = 21) patients. Results (1) In healthy, the thalamus-SMN FC showed a quadratic correlation with SN-BG/thalamus FC and a linear negative correlation with RN-BG/thalamus FC. Accordingly, the SN-related FC appears to enable the thalamus-SMN coupling, while the RN-related FC affects it favoring anti-correlation. (2) In BD, mania showed an increase in thalamus-SMN FC toward positive values (ie, thalamus-SMN abnormal coupling) paralleled by reduction of RN-BG/thalamus FC. By contrast, inhibited depression showed a decrease in thalamus-SMN FC toward around-zero values (ie, thalamus-SMN disconnection) paralleled by reduction of SN-BG/thalamus FC (and RN-BG/thalamus FC). The results were replicated in independent HC and BD datasets. Conclusions These findings suggest an abnormal relationship of SMN with neurotransmitters-related areas via subcortical-cortical loops in mania and inhibited depression, finally resulting in psychomotor alterations.

The neurotransmitters GABA and glutamate have been suggested to play a role in Major Depressive Disorder (MDD) through an imbalance between cortical inhibition and excitation. This effect has been highlighted in higher brain areas, such as the prefrontal cortex, but has also been posited in basic sensory cortices. Based on this, magnetic resonance spectroscopy (MRS) was used to investigate potential changes to GABA+ and glutamate+glutamine (Glx) concentrations within the occipital cortex in MDD patients (n = 25) and healthy controls (n = 25). No difference in occipital GABA+ or Glx concentrations, nor in the GABA+/Glx ratio, was found between groups. An analysis of an extended MDD patient and unmatched control dataset (n = 90) found no correlation between metabolite concentrations and depressive symptoms. These results were integrated with prior studies through metabolite-specific meta-analyses, revealing no difference in occipital GABA and Glx concentrations between patients and controls. An effect of publication year on GABA group differences was found, suggesting that previously reported results may have been artifacts of measurement accuracy. Taken together, our results suggest that, contrary to some prior reports, MRS measurements of occipital GABA and Glx do not differ between MDD patients and controls.

Sertraline is one of the most commonly prescribed antidepressants. Major depressive disorder (MDD) is characterized by spontaneous thoughts that are laden with negative affect-a "malignant sadness". Prior neuroimaging studies have identified abnormal resting-state functional connectivity (rsFC) in the spontaneous brain networks of MDD patients. But how antidepressant medication acts to relieve the experience of depression as well as adjust its associated spontaneous networks and mood-regulation circuits remains an open question. In this study, we recruited 22 drug-naïve MDD patients along with 35 normal controls and investigated whether the functional integrity of cortical networks associated with spontaneous thoughts is modulated by sertraline treatment. We attempted to predict post-treatment effects based upon what we observed in the pre-treatment rsFC of drug-naïve MDD patients. In the result, we demonstrated that (1) after the sertraline treatment, the medial temporal lobe of default network (DNMTL) and mood regulation pathway-the fronto-parietal control network (FPCN), the thalamus, and the salience network (SN)-were restored to normal connectivity, relative to the pre-treatment condition; however, the altered connections of FPCN-core DN (DNCORE), FPCN-SN, and intra-FPCN among MDD patients remained impaired; (2) thalamo-prefrontal connectivity provides moderate predictive power (r2 = 0.63) for the effectiveness of sertraline treatment. In summary, our findings contribute to a body of evidence that suggests salubrious effects of sertraline treatment primarily involve the FPCN-thalamus-SN pathway. The pre-treatment rsFC in this pathway could serve as a predictor of sertraline treatment outcome.

Resting state networks comprise several brain regions that exhibit complex patterns of interaction. Switching from eyes closed (EC) to eyes open (EO) during the resting state modifies these patterns of connectivity, but precisely how these change remains unclear. Here we use functional magnetic resonance imaging to scan healthy participants in two resting conditions (viz., EC and EO). Seven resting state networks were chosen for this study: salience network (SN), default mode network (DMN), central executive network (CEN), dorsal attention network (DAN), visual network (VN), motor network (MN) and auditory network (AN). We performed functional connectivity (FC) analysis for each network, comparing the FC maps for both EC and EO. Our results show increased connectivity between most networks during EC relative to EO, thereby suggesting enhanced integration during EC and greater modularity or specialization during EO. Among these networks, SN is distinctive: during the transition from EO to EC it evinces increased connectivity with DMN and decreased connectivity with VN. This change might imply that SN functions in a manner analogous to a circuit switch, modulating resting state relations with DMN and VN, when transitioning between EO and EC.

Background Neuroimaging and lesion studies suggested that the dorsolateral prefrontal and posterior parietal cortices mediate visual metacognitive awareness. The causal evidence provided by non-invasive brain stimulation, however, is inconsistent. Objective/hypothesis Here we revisit a major figure discrimination experiment adding a new Kanizsa figure task trying to resolve whether bilateral continuous theta-burst transcranial magnetic stimulation (cTBS) over these regions affects perceptual metacognition. Specifically, we tested whether subjective visibility ratings and/or metacognitive efficiency are lower when cTBS is applied to these two regions in comparison to an active control region. Methods A within-subjects design including three sessions spaced by one-week intervals was implemented. In each session, every participant was administered bilateral cTBS to either prefrontal, control or parietal cortices. Two concurrent tasks were performed, a real and an illusory figure task, stabilising objective performance with use of an adaptive staircase procedure. Results When performing the replicated task, cTBS was found insufficient to disrupt neither visibility ratings nor metacognitive efficiency. However, with use of Kanizsa style illusory figures, cTBS over the dorsolateral prefrontal, but not over the posterior parietal cortex, was observed to significantly diminish metacognitive efficiency. Conclusion(s) Real and illusory figure tasks demonstrated different cTBS effects. A possible explanation is the involvement of the prefrontal cortex in the creation of expectations, which is necessary for efficient metacognition. Failure to replicate previous findings for the real figure task, however, cannot be said to support, conclusively, the notion that these brain regions have a causal role in metacognitive awareness. This inconsistent finding may result from certain limitations of our study, thereby suggesting the need for yet further investigation.

Previous research has suggested that bodily signals from internal organs are associated with diverse cortical and subcortical processes involved in sensory-motor functions, beyond homeostatic reflexes. For instance, a recent study demonstrated that the preparation and execution of voluntary actions, as well as its underlying neural activity, are coupled with the breathing cycle. In the current study, we investigated whether such breathing-action coupling is limited to voluntary motor action or whether it is also present for mental actions not involving any overt bodily movement. To answer this question, we recorded electroencephalography (EEG), electromyography (EMG), and respiratory signals while participants were conducting a voluntary action paradigm including self-initiated motor execution (ME), motor imagery (MI), and visual imagery (VI) tasks. We observed that the voluntary initiation of ME, MI, and VI are similarly coupled with the respiration phase. In addition, EEG analysis revealed the existence of readiness potential (RP) waveforms in all three tasks (i.e., ME, MI, VI), as well as a coupling between the RP amplitude and the respiratory phase. Our findings show that the voluntary initiation of both imagined and overt action is coupled with respiration, and further suggest that the breathing system is involved in preparatory processes of voluntary action by contributing to the temporal decision of when to initiate the action plan, regardless of whether this culminates in overt movements.

Subjective perception of sleep is not necessarily consistent with electroencephalography (EEG) indications of sleep. The mismatch between subjective reports and objective measures is often referred to as “sleep state misperception.” Previous studies evince that this mismatch is found in both patients with insomnia and in normal sleepers, but the neurophysiological mechanism remains unclear. The aim of the study is to explore the neurophysiological basis of this mechanism, from the perspective of both EEG power and functional magnetic resonance imaging (fMRI) fluctuations. Thirty-six healthy young adults participated in the study. Simultaneous EEG and fMRI recordings were conducted while the participants were trying to fall asleep in an MRI scanner at approximately 9:00 pm. They were awakened after achieving stable N1 or N2 sleep, or after 90 min without falling into stable sleep. Next they were asked to recall their conscious experiences from the moment immediately prior to awakening. Sixty-one instances of scheduled awakenings were collected: 21 of these after having achieved stable stage N2 sleep; 12, during stage N1 sleep; and, 20 during the waking state. Relative to those awakenings without subjective–objective discrepancy (n = 27), these awakenings with discrepancy (n = 14) were associated with lower θ power, as well as higher α, β, and γ power. Moreover, we found that participants who exhibited the discrepancy, compared with those who did not, evinced a higher amplitude of low-frequency fluctuation levels in the prefrontal cortex. These results lend support to the conjecture that the subjective–objective discrepancy is associated with central nervous system hyperarousal.

For millennia self has been conjectured to be necessary for consciousness. But scant empirical evidence has been adduced to support this hypothesis. Inconsistent explications of “self” and failure to design apt experiments have impeded progress. Advocates of phenomenological psychiatry, however, have helped explicate “self,” and employed it to explain some psychopathological symptoms. In those studies, “self” is understood in a minimalist sense, sheer “for-me-ness.” Unfortunately, explication of the “minimal self” (MS) has relied on conceptual analysis, and applications to psychopathology have been hermeneutic, allowing for many degrees of interpretive latitude. The result is that MS’s current scientific status is analogous to that of the “atom,” at the time when “atom” was just beginning to undergo transformation from a philosophical to a scientific concept. Fortunately, there is now an opportunity to promote a similar transformation for “MS.” Discovery of the brain’s Default Mode Network (DMN) opened the door to neuroimaging investigations of self. Taking the DMN and other forms of intrinsic activity as a starting point, an empirical foothold can be established, one that spurs experimental research and that enables extension of research into multiple phenomena. New experimental protocols that posit “MS” can help explain phenomena hitherto not thought to be related to self, thereby hastening development of a mature science of self. In particular, targeting phenomena wherein consciousness is lost and recovered, as in some cases of Unresponsive Wakefulness Syndrome (UWS), allow for design of neuroimaging probes that enable detection of MS during non-conscious states. These probes, as well as other experimental protocols applied to NREM Sleep, General Anesthesia (GA), and the waking state, provide some evidence to suggest that not only can self and consciousness dissociate, MS might be a necessary precondition for conscious experience. Finally, these findings have implications for the science of consciousness: it has been suggested that “levels of consciousness” (LoC) is not a legitimate concept for the science of consciousness. But because we have the conceptual and methodological tools with which to refine investigations of MS, we have the means to identify a possible foundation—a bifurcation point—for consciousness, as well as the means by which to measure degrees of distance from that foundation. These neuroimaging investigations of MS position us to better assess whether LoC has a role to play in a mature science of consciousness.

Even when brain scans fail to detect a striate lesion, functional evidence for blindsight can be adduced. In the aftermath of an automobile accident, JK became blind. Results of ophthalmic exams indicated that the blindness must be cortical. Nevertheless, multiple MRI scans failed to detect structural damage to the striate cortex. Prior to the accident JK had been an athlete; after the accident he retained some athletic abilities, arousing suspicions that he might be engaged in fraud. His residual athletic abilities—e.g., hitting a handball or baseball, or catching a Frisbee—coupled with his experienced blindness, suggested blindsight. But due to the apparent absence of striate lesions, we designed a series of tasks for temporal and spatial dimensions in an attempt to detect functional evidence of his disability. Indeed, test results revealed compelling neural evidence that comport with his subjective reports. This spatiotemporal task-related method that includes contrasts with healthy controls, and detailed understanding of the patient's conscious experience, can be generalized for clinical, scientific and forensic investigations of blindsight.

Background: Rumination, a tendency to focus on negative self-related thoughts, is a central symptom of depression. Studying the self-related aspect of such symptoms is challenging because of the need to distinguish self effects from the emotional content of task stimuli. This study employed an emotionally neutral self-related paradigm to investigate possible altered self-processing in depression and its link to rumination. Methods: People with major depressive disorder (n = 25) and controls (n = 25) underwent task-based electro-encephalogram recording. We studied late event-related potentials, along with low-frequency oscillatory power. We compared electroencephalogram metrics between groups and correlated them with depressive symptoms and reported rumination. Results: Participants with major depressive disorder displayed a difference in late positive potentials across frontocentral electrodes between self-related and non-self-related conditions. We found no such difference in controls. The magnitude of this difference was positively correlated with depressive symptoms and reported rumination. Participants with major depressive disorder also had elevated theta oscillation power at central electrodes in self-related conditions, a finding that we did not see in controls. Limitations: Patients with major depressive disorder were medicated at the time of the study. The group studied was primarily female, so the observed effects may have been sex-specific. Conclusion: Rumination appears to be linked to altered self-related processing in depression, independent of stimuli-related emotional confounds. This connection between self-related processing and depression may point to a self disorder as a core component of depression.

The brain’s intrinsic activity plays a fundamental role in its function. In normal conditions this activity is responsive to behavioural context, changing as an individual switches between directed tasks and task‐free conditions. A key feature of such changes is the movement of the brain between corresponding critical and sub‐critical states, with these dynamics supporting efficient cognitive processing. Breakdowns in processing efficiency can occur, however, in brain disorders such as depression. It was therefore hypothesised that depressive symptoms would be related to reduced intrinsic activity responsiveness to changes in behavioural state. This was tested in a mixed group of major depressive disorder patients (n = 26) and healthy participants (n = 37) by measuring intrinsic EEG activity temporal structure, quantified with detrended fluctuation analysis (DFA), in eyes‐closed and eyes‐open task‐free states and contrasting between the conditions. The degree to which DFA values changed between the states was found to be negatively correlated with depressive symptoms. DFA values did not differ between states at all in those with higher symptom levels, meaning that the brain remained in a less flexible sub‐critical condition. This sub‐critical condition in the eyes‐closed state was further found to correlate with levels of maladaptive rumination. This may reflect a general cognitive inflexibility resulting from a lack in neural activity reactivity that may predispose people to overly engage in self‐directed attention. These results provide an initial link between intrinsic activity reactivity and psychological features found in psychiatric disorders.

According to Rosenthal’s Higher-Order Thought (HOT) theory of consciousness, first-order mental states become conscious only when they are targeted by HOTs that necessarily represent the states as belonging to self. On this view a state represented as belonging to someone distinct from self could not be a conscious state. Rosenthal develops this view in terms of what he calls the ‘thin immunity principle’ (TIP). According to TIP, when I experience a conscious state, I cannot be wrong about whether it is I who I think is in that state. We first suggest that TIP is a direct consequence of the HOT theory. Next we argue that somatoparaphrenia—a pathology in which sensations are sometimes represented as belonging to other people—shows that TIP can be violated. This violation of TIP in turn shows that the HOT theory’s claim that conscious states are necessarily represented as belonging to self is in error. Rosenthal’s attempt to account for pathological cases is found to be inadequate when applied to somatoparaphrenia, and other possible defenses are also shown to be incapable of preserving TIP. We further conclude by suggesting that the HOT theory’s failing in this regard is not a failing that is peculiar to this theory of consciousness.

Sydney Shoemaker, developing an idea of Wittgenstein’s, argues that we are immune to error through misidentification relative to the first-person pronoun. Although we might be liable to error when “I” (or its cognates) is used as an object, we are immune to error when “I” is used as a subject (as when one says, “I have a toothache”). Shoemaker claims that the relationship between “I” as-subject and the mental states of which it is introspectively aware is tautological: when, say, we judge that “I feel pain,” we are tautologically aware that feels pain is instantiated and that it is instantiated in oneself. Moreover, he contends that this relationship holds not just for bodily sensations, but also for the sense of agency and for visual perception. But we deny that this relationship is tautological; instead, we treat Shoemaker’s principle (IEM) as a hypothesis. We then proceed to show that certain pathological states and experimentally-induced illusions can be adduced to show that IEM describes not a necessary relationship but a contingent relationship, one that sometimes fails to obtain. That we are not immune to error in the way Shoemaker describes has grave consequences for many aspects of his ideas concerning the first-person perspective. In the course of arguing that these empirical phenomena count against IEM, we also show that not only can the content of conscious experience be misrepresented, so too can the subject: that is, not only can the what of conscious experience be misrepresented, so too can the who.

According to Allen Wood’s “procedural principle” we should believe only that which can be justified by evidence, and nothing more. He argues that holding beliefs which are not justified by evidence diminishes our self-respect and corrupts us, both individually and collectively. Wood’s normative and descriptive views as regards belief are of a piece with the received view which holds that beliefs aim at the truth. This view I refer to as the Truth-Tracking View (TTV). I first present a modest version of TTV, one which is sensitive to standard criticisms and one which is fully consistent with the procedural principle. I then raise some doubts about TTV by considering both anecdotal cases and empirical studies. These studies suggest that certain types of belief are designed to aim away from truth, in limited, carefully calibrated ways. Moreover, it seems to be the case that selectively aiming away from the truth is important for human well-being and performance. Beliefs that are designed to aim away I dub “Tertullian” beliefs (t-beliefs). I then limn the distinguishing characteristics of t-belief and proceed to evaluate the procedural principle in light of the evidence which suggests that t-belief plays an important role in our cognitive economy. Next I argue that t-beliefs might be essential to the maintenance of self-respect and that they do not corrupt in the way that Wood claims. Finally, I argue that the fate of Wood’s procedural principle will be determined by the results of further empirical research— sociological, psychological, and neuroscientific.

Time is an essential feature in bipolar disorder (BP). Manic and depressed BP patients perceive the speed of time as either too fast or too slow. The present article combines theoretical and empirical approaches to integrate phenomenological, psychological, and neuroscientific accounts of abnormal time perception in BP. Phenomenology distinguishes between perception of inner time, ie, self-time, and outer time, ie, world-time, that desynchronize or dissociate from each other in BP: inner time speed is abnormally slow (as in depression) or fast (as in mania) and, by taking on the role as default-mode function, impacts and modulates the perception of outer time speed in an opposite way, ie, as too fast in depression and too slow in mania. Complementing, psychological investigation show opposite results in time perception, ie, time estimation and reproduction, in manic and depressed BP. Neuronally, time speed can be indexed by neuronal variability, ie, SD. Our own empirical data show opposite changes in manic and depressed BP (and major depressive disorder [MDD]) with abnormal SD balance, ie, SD ratio, between somatomotor and sensory networks that can be associated with inner and outer time. Taken together, our combined theoretical-empirical approach demonstrates that desynchronization or dissociation between inner and outer time in BP can be traced to opposite neuronal variability patterns in somatomotor and sensory networks. This opens the door for individualized therapeutic “normalization” of neuronal variability pattern in somatomotor and sensory networks by stimulation with TMS and/or tDCS.

It is becoming increasingly difficult for those who engage in ethical analysis to ignore evolution and neuroscience. The kind of creature that we are and that we have evolved to be matters when determining how we ought to live. There is still a need to aim for a reflective equilibrium that includes reflection over not straightforwardly empirical issues. It would, for example, be inaccurate to say that "good" just means "highly evolved." But it does turn out to be the case that many questions pivotal to ethical theorizing are straightforwardly empirical. And, to a large extent, ethics can be treated as a kind of applied science, one that aims to encourage personal and social flourishing. Of course just what counts as "flourishing" is a matter that will also require a healthy dose of reflective equilibrium. Be that as it may, the best philosophers of the 21st century do what the best philosophers of previous centuries did: they draw upon the resources available to them during the era in which they work. In this era that includes evolutionary biology and neuroscience.

"Rationality: Contexts and Constraints" is an interdisciplinary reappraisal of the nature of rationality. In method, it is pluralistic, drawing upon the analytic approaches of philosophy, linguistics, neuroscience, and more. These methods guide exploration of the intersection between traditional scholarship and cutting-edge philosophical or scientific research. In this way, the book contributes to development of a suitably revised, comprehensive understanding of rationality, one that befits the 21st century, one that is adequately informed by recent investigations of science, pathology, non-human thought, emotion, and even enigmatic Chinese texts that might previously have seemed to be expressions of irrationalism. Addresses recent challenges and Identifies a direction for future research on rationalityInvestigates the relationship between rationality and mental disorders, such as delusion and depressionAssesses reasoning in artificial intelligence and nonhuman animalsReflects on ancient Chinese Philosophy and possible cultural differences in human psychology Employs philosophical reflection, along with linguistic, probabilistic, and logical techniques.

There is a distinctive form of existential anxiety, neuroexistential anxiety, which derives from the way in which contemporary neuroscience provides copious amounts of evidence to underscore the Darwinian message—we are animals, nothing more. One response to this 21st century existentialism is to promote Eudaimonics, a version of ethical naturalism that is committed to promoting fruitful interaction between ethical inquiry and science, most notably psychology and neuroscience. We argue that philosophical reflection on human nature and social life reveals that while working to be and remain biologically fit, humans also seek meaning in a way that conforms to a pattern recognized by Plato. We argue that human beings should seek “the good,” “the true,” and “the beautiful”; moreover, the proper measure of human flourishing is the degree to which humans achieve these three, in a maximally harmonious way. One potential problem with this view, however, is that it might privilege the role of truth, such that if there is a conflict among these three, what is good or beautiful should yield to what is true. But this seems to conflict with evidence from neuroscience and psychology (e.g. the study of positive illusions) which suggests that people with a tendency to form and harbor certain false beliefs tend to more easily achieve eudaimonia than do those for whom truth takes precedence in all domains. We argue that this conflict is only apparent: the false beliefs in question are not literally beliefs; instead, they are an amalgam of belief and desire, an amalgam that we dub, tertullian beliefs (or, t-beliefs). Among other things, what is distinctive about t-beliefs is that they are able to change the world, in certain specific ways, such that, strictly speaking, it would be erroneous to say of them that they aim away from the truth. Paradoxically, it is because they seem to aim away from the truth, that they are sometimes able to succeed in changing the world so that it matches what we desire, or, what we t-believe.