The psychological neuroscience of depression: implications for understanding effects of deep brain stimulation

In this article it is suggested that current psychological theories of depression presuppose that this condition will develop as a result of a vicious circle involving negatively biased communication between systems of emotional stress-/alarm-signaling, executive functions and mood regulation. These systems may from a neuroanatomical point of view be located in the limbic system, the orbitofrontal and lateral prefrontal cortex and the hypothalamus-pituitary-adrenal (HPA-) axis respectively. The theoretical and practical implications of this model for the understanding of pharmacological treatments of depression are briefly discussed and this theory is related to the catecholamine hypothesis of depression. The model is furthermore discussed in relation to deep brain stimulation (DBS) of treatment resistant major depression. Similarities and differences between this perspective and the one advocated by the "homeostatic theory" of depression are discussed. It is concluded that a topographical psychological theory may offer a useful heuristic in thinking about depression and that it offers several testable predictions about treatments of the disorder.     

Mechanisms and the current state of deep brain stimulation in neuropsychiatry

Deep brain stimulation (DBS) is established as a therapy for movement disorders, and it is an investigational treatment in other neurologic conditions. DBS precisely targets neuroanatomical targets deep within the brain that are proposed to be centrally involved in the pathophysiology of some neuropsychiatric illnesses. DBS is nonablative, offering the advantages of reversibility and adjustability. This might permit therapeutic effectiveness to be enhanced or side effects to be minimized. Preclinical and clinical studies have shown effects of DBS locally, at the stimulation target, and at a distance, via actions on fibers of passage or across synapses. Although its mechanisms of action are not fully elucidated, several effects have been proposed to underlie the therapeutic effects of DBS in movement disorders, and potentially in other conditions as well. The mechanisms of action of DBS are the focus of active investigation in a number of clinical and preclinical laboratories. As in severe movement disorders, DBS may offer a degree of hope for patients with intractable neuropsychiatric illness. It is already clear that research intended to realize this potential will require a very considerable commitment of resources, energy, and time across disciplines including psychiatry, neurosurgery neurology, neuropsychology, bioengineering, and bioethics. These investigations should proceed cautiously.     

A review of the treatment for refractory obsessive-compulsive disorder: from medicine to deep brain stimulation

This article provides an overview of the etiology, epidemiology, and first-line treatment options for obsessive-compulsive disorder (OCD). The subject of treatment-resistant and treatment-refractory OCD is then discussed, including a definition of these often-debated terms, and the latest treatment options delineated. This includes a review of the latest research concerning the pharmacological agents that have been studied as monotherapy or augmenting agents for the treatment of OCD, the use of experimental medications and procedures, treatment with reversible, minimally invasive procedures, such as vagal nerve stimulation and transcranial magnetic stimulation, invasive but the potentially reversible deep brain stimulation, and irreversible lesioning with ablative psychosurgery. A discussion of the role of psychotherapy in the treatment of OCD is also included.     

Modulation of tremor amplitude during deep brain stimulation at different frequencies

Rest tremor was quantified in the index finger tip of 16 patients with Parkinson's disease (PD) receiving deep brain stimulation (DBS) of the ventro-intermediate nucleus (Vim) of the thalamus, the subthalamic nucleus (STN), or the internal part of the globus pallidus (GPi) while being off L-dopa for 12h. Clinically, without DBS, tremor amplitude varied from absent to high. Tremor was recorded continuously for about 5 min under three conditions of DBS repeated twice, namely, effective frequency (E), ineffective frequency (I), and no DBS (O). No changes in tremor were observed across conditions in subjects with little or no tremor. However, in subjects with moderate to large amplitude tremor, DBS decreased tremor amplitude to near normal values within a few seconds. Generally, transitions were progressive and occurred with a varying time delay. Occasionally, tremor escaped from control regardless of the stimulation condition considered. In some cases tremor amplitude in one condition appeared to depend on the preceding condition. Finally, the results were reproducible on two consecutive days. We conclude that tremor control with DBS follows specific dynamical rules, which must be compatible with the hypotheses proposed regarding the underlying mechanisms of DBS.     

Outsourcing the deep self: Deep self discordance does not explain away intuitions in manipulation arguments

According to manipulation arguments for incompatibilism, manipulation might undermine an agent’s responsibility even when the agent satisfies plausible compatibilist conditions on responsibility. According to Sripada (2012 Sripada, C. (2012). What makes a manipulated agent unfree? Philosophy and Phenomenological Research, 85, 563–593.[Crossref], [Web of Science ®] , [Google Scholar]), however, empirical data suggest that people take manipulation to undermine responsibility largely because they think that the manipulated act is in discord with the agent’s “deep self,” thus violating the plausible compatibilist condition of deep self concordance. This paper defends Sripada’s general methodological approach but presents data that strongly suggest that, contrary to Sripada’s contention, most of the effect of manipulation on attributions of moral responsibility is unmediated by worries about inadequate information or deep self discordance. Instead, it depends largely on worries that the action is ultimately explained by factors outside the agent’s control, just as proponents of manipulation arguments have proposed. More generally, data suggest that judgments of deep self discordance are themselves explained by worries about responsibility, and that the everyday notion of what an agent wants or is “deep down” is sensitive not only to the agent’s internal psychological structure, but also its source. This casts some doubt on recent claims about the explanatory role of deep self judgments.     

Lessons learned in deep brain stimulation for movement and neuropsychiatric disorders

The introduction of deep brain stimulation (DBS) as a treatment for medication-refractory essential tremor in the late 1980s revealed, for the first time, that "chronically" implanted brain hardware had the potential to modulate neurologic function with surprisingly low morbidity. Over time, the therapeutic promise of DBS has become evident in Parkinson's disease and dystonia. In some experienced centers, complex tremor disorders, such as posttraumatic Holmes tremor and the tremor of multiple sclerosis, are being increasingly targeted. More recently, other indications, including obsessive-compulsive disorder, Tourette's syndrome, major depression, and chronic pain, have been proposed. As the field has expanded, our knowledge about potential cognitive side effects of DBS has also expanded. This article reviews the current knowledge regarding the impact of stimulation of the subthalamic nucleus, globus pallidus internus, and ventralis intermedius nucleus of the thalamus on symptoms in essential tremor, Parkinson's disease, and dystonia. Also discussed are the emerging targets, what is known about the cognitive sequelae of DBS, and what has been learned about the complications and therapeutic failures.     

The role of brain stimulation priming effects in self-deprivation

Choice of brain stimulation reward (BSR) over biologically necessary substances in some self-stimulating animals is referred to as self-deprivation. In several recent papers, it has been argued that this phenomenon is produced by the rewarding aspects of the brain stimulation. This conclusion is partially based on data showing that self-deprivation and brain stimulation reward increase and decrease in a similar manner in response to changes in the brain stimulation parameters. However, the priming aspects of the brain stimulation also fluctuate with changes in stimulation parameters. Therefore, changes in the priming rather than the rewarding aspects of the brain stimulation could be responsible for self-deprivation. To determine whether the priming effects of brain stimulation play an important role in self-deprivation, rats with bipolar stimulating electrodes were given the choice between BSR and food. Time-outs were enforced within each BSR/food competition session. Since priming effects decay over time, increasing time-out length should have decreased self-deprivation due to decay of priming. It was found that time-out length did not affect the degree of self-deprivation. It was concluded that self-deprivation is not mediated by the priming aspects of brain stimulation.     

Health-related quality of life in Parkinson's disease after pallidotomy and deep brain stimulation

This study explored the multidimensional outcome of three neurosurgical interventions for Parkinson's disease (PD): pallidotomy (N = 23), pallidal deep brain stimulation (DBS) (N = 9), and thalamic DBS (N = 7). All patients completed the Sickness Impact Profile (SIP) and the Beck Depression Inventory. Pallidotomy patients also completed the Profile of Mood States, the Beck Anxiety Inventory, and a disease-specific quality of life (QOL) measure, the Parkinson's Disease Questionnaire (PDQ-39). Three months after surgery, all neurosurgical groups showed significant improvements in mood and function, including physical, psychosocial, and overall functioning. Pallidal DBS and pallidotomy patients who completed additional QOL measures reported decreased anxiety and tension, increased vigor, improved mobility and ability to perform activities of daily living, and decreased perceived stigma. Psychosocial dysfunction scores from the SIP were related to depressed mood both at baseline (r = .42) and at followup (r = .45), but the physical dysfunction subscale was not related to mood at either time point, suggesting that disruption of social relationships due to PD may have more impact on affective distress than physical symptoms alone. Results suggest that neurosurgical interventions for PD improve disabling PD motor symptoms and also improve several domains of quality of life.     

The self in deep ecology: A response to Watson

ABSTRACT

Richard Watson maintains that deep ecology suffers from an internal contradiction and should therefore be rejected. Watson contends that deep ecology claims to be non-anthropocentric while at the same time is committed to setting humans apart from nature, which is inherently anthropocentric. I argue that Watson’s objection arises out of a fundamental misunderstanding of how deep ecologist’s conceive of the ‘Self.’ Drawing on resources from Buddhism, I offer an understanding of the ‘Self’ that is fully consistent with deep ecology, and does not lead to the anthropocentric contradiction that Watson identifies. The paper will proceed as follows: First, I articulate Watson’s objection, and briefly discuss the traditional deep ecology position. Next, I turn to a discussion of the ‘Self’ and show that there are conceptions of human nature that are not separate from ‘Nature.’ It will thus be shown that deep ecology is not inconsistent and need not be rejected.     

Autobiographical memory and the self in time: brain lesion effects, functional neuroanatomy, and lifespan development

Autobiographical remembering reflects an advanced state of consciousness that mediates awareness of the self as continuous across time. In naturalistic autobiographical memory, self-aware recollection of temporally and spatially specific episodes and generic factual information (both public and personal) operate in tandem. Evidence from both laboratory and real-life studies, however, suggests that these two processes can be dissociated. This paper reviews aging, lesion, and functional neuroimaging research on the anatomical substrates of autobiographical memory processes using a new measure, the Autobiographical Interview, and prospective collection of autobiographical material. Results indicate that autobiographical recollection is mediated by a distributed fronto-temporo-parietal system, with the anteromedial prefrontal cortex positioned to integrate sensory information with self-specific information. The emergence of autobiographical recollection at around age four coincides with the timing of prefrontal regressive cortical and progressive white matter changes that may support the development of this high-level capacity.     

Watching Eyes effects: When others meet the self

The perception of direct gaze—that is, of another individual’s gaze directed at the observer—is known to influence a wide range of cognitive processes and behaviors. We present a new theoretical proposal to provide a unified account of these effects. We argue that direct gaze first captures the beholder’s attention and then triggers self-referential processing, i.e., a heightened processing of stimuli in relation with the self. Self-referential processing modulates incoming information processing and leads to the Watching Eyes effects, which we classify into four main categories: the enhancement of self-awareness, memory effects, the activation of pro-social behavior, and positive appraisals of others. We advance that the belief to be the object of another’s attention is embedded in direct gaze perception and gives direct gaze its self-referential power. Finally, we stress that the Watching Eyes effects reflect a positive impact on human cognition; therefore, they may have a therapeutic potential, which future research should delineate.     

Detecting contingency: A key to understanding development of self and social cognition

Abstract:  Detecting contingency between self-produced actions and the consequences plays a crucial role for basic cognitive functions, such as construction of self body-image and tool-use. This paper reviews our recent studies focusing on the temporal aspect of contingency. Three studies concerning the detection of proprioceptive-visual contingency in infants, children and adults are summarized. All of these studies use delayed self-image as a tool to investigate the temporal aspect of contingency detection. Based on the results of these studies and related preceding research, the paper proposes the ubiquity of a contingency detector among the development of self and social interaction.     

Some aspects of self aversive stimulation in the hooded rat

Three hooded rats were trained to bar press for variable-ratio liquid reinforcement after which an electric shock was delivered following the response. Initially, the shock was presented on a FR 100 basis but the frequency was gradually increased until all responses were punished. Finally, a partial extinction procedure was conducted to determine if the shock resulted in increased bar pressing. No durable suppression of responding occurred, although one subject's rate was reduced during continuous shock. The overall trend for the three animals was one of increased responding. Changes in the pattern of responding were also observed suggesting that the suppressive effects of the punishment were largely restricted to the first response following reinforcement. Increased responding as a function of shock reintroduction during extinction was also observed.     

The battle within the self, 1: An existential framework for understanding personality disorders

A new phenomenologically based model for understanding personality disorders is presented. This model draws upon the existential concepts of Dasein and pitch to explain how individuals with personality disorders have extremely constricted and rigid experiences of the world. When they were children, these individuals internalized and retained hypercritical, sadistic parental messages. Such covert parental voices are misidentified as rational evaluations by these patients who are deficient in their capacity to engage in rational self-evaluation. When these individuals are encouraged to observe and report upon the internalized self-attacks, their observing ego is strengthened and an effective groundwork is set for ultimate changes in behavior.     

Synergistic effects of ethanol and cocaine on brain stimulation reward.

The effects of two widely abused drugs, ethanol and cocaine, were examined alone and in combination on intracranial reward processes. In agreement with previous research, higher doses of both cocaine and ethanol alone produced facilitation of behavior maintained by brain stimulation reward. Low intraperitoneal doses of ethanol and cocaine, which alone did not affect performance, were found to reduce stimulation reward threshold and modestly increase response rate. The enhancement of brain stimulation reward by the combination of ethanol and cocaine suggests that both drugs may produce their rewarding effects through common neuronal substrates and that they may potentiate the abuse of each other.