Multimodal single-neuron, intracranial EEG, and fMRI brain responses during movie watching in human patients.

We present a multimodal dataset of intracranial recordings, fMRI, and eye tracking in 20 participants during movie watching. Recordings consist of single neurons, local field potential, and intracranial EEG activity acquired from depth electrodes targeting the amygdala, hippocampus, and medial frontal cortex implanted for monitoring of epileptic seizures. Participants watched an 8-min long excerpt from the video "Bang! You're Dead" and performed a recognition memory test for movie content. 3 T fMRI activity was recorded prior to surgery in 11 of these participants while performing the same task. This NWB- and BIDS-formatted dataset includes spike times, field potential activity, behavior, eye tracking, electrode locations, demographics, and functional and structural MRI scans. For technical validation, we provide signal quality metrics, assess eye tracking quality, behavior, the tuning of cells and high-frequency broadband power field potentials to familiarity and event boundaries, and show brain-wide inter-subject correlations for fMRI. This dataset will facilitate the investigation of brain activity during movie watching, recognition memory, and the neural basis of the fMRI-BOLD signal.

Caltech Conte Center, a multimodal data resource for exploring social cognition and decision-making.

This data release of 117 healthy community-dwelling adults provides multimodal high-quality neuroimaging and behavioral data for the investigation of brain-behavior relationships. We provide structural MRI, resting-state functional MRI, movie functional MRI, together with questionnaire-based and task-based psychological variables; many of the participants have multiple datasets from retesting over the course of several years. Our dataset is distinguished by utilizing open-source data formats and processing tools (BIDS, FreeSurfer, fMRIPrep, MRIQC), providing data that is thoroughly quality checked, preprocessed to various extents and available in multiple anatomical spaces. A customizable denoising pipeline is provided as open-source code that includes tools for the generation of functional connectivity matrices and initialization of individual difference analyses. Behavioral data include a comprehensive set of psychological assessments on gold-standard instruments encompassing cognitive function, mood and personality, together with exploratory factor analyses. The dataset provides an in-depth, multimodal resource for investigating associations between individual differences, brain structure and function, with a focus on the domains of social cognition and decision-making.

Commentary on "Bosch-Boonstra-Schaaf Optic Atrophy Syndrome Presenting as New-Onset Psychosis in a 32-Year-Old Man: A Case Report and Literature Review".

Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS) is a recently described autosomal dominant disorder caused by mutations in the nuclear receptor subfamily 2 group F member 1 (NR2F1) gene. Its common features include optic atrophy and/or hypoplasia, developmental delay, intellectual disability, attention deficit disorder, autism spectrum disorder, seizures, hearing defects, spasticity, hypotonia, and thinning of the corpus callosum. Mitochondrial involvement has also been described with BBSOAS. Currently, 31 cases of BBSOAS have been described in the literature. Here we report a case of undiagnosed BBSOAS presenting as psychosis in a 32-year-old man with a history of bilateral optic nerve atrophy, intellectual disability, epilepsy, and mitochondrial complex I abnormality on muscle biopsy. Whole-genome sequencing identified a heterozygous de novo nonsense mutation in the NR2F1 gene [c.253 G>T (guanine to thymine mutation in coding position 253) in exon 1, p.E85X variant (GAG>TAG) (glutamic acid to stop codon mutation; protein truncated to 85 amino acids)]. A pathogenic nonsense mutation has not previously been reported in the literature in association with BBSOAS and represents an expansion of clinically relevant variants. Psychosis has also not been previously reported in this syndrome and may represent a phenotypic expansion of BBSOAS, a manifestation of prolonged disease, or a result of disease management.

Commentary on "Synchrony Between Bipolar Mood Cycles and Lunar Tidal Cycles Ended After Initiation of Light Treatment and Treatment of Hypothyroidism".

According to a recent report, mood cycles in a group of patients with rapid cycling bipolar disorder oscillated in synchrony with lunar gravimetric tides. Mood switches in a 67-year-old woman with rapid cycling bipolar II disorder on lithium maintenance treatment were assessed with a χ periodogram and a χ analysis of the mood switches in relation to the lunar tidal cycle. During a period when she was treated with nortriptyline and her thyroid-stimulating hormone levels were elevated, her mood switches had a significant (P<0.05) 29- to 30-day periodicity, and the χ analysis showed that the switches were distributed nonrandomly in relation to the spring-neap lunar tidal cycle (P<0.0001); 14 of 15 switches occurred within 2 days of the spring tides. After nortriptyline was discontinued, thyroid-stimulating hormone levels were normalized with treatment with levothyroxine, and consistent bright light treatment was started, the synchrony between mood cycles and lunar cycles disappeared, and rapid cycling eventually stopped. The possibility that lunar mood cycling is sometimes contingent on antidepressant treatment, decreased thyroid function, and certain types of light-dark cycles needs to be considered in future research on lunar tidal influences on the course of bipolar illness.

Commentary on "Are We Missing Subtle Forms of Anti-N-Methyl-D-Aspartate Encephalitis With the Current Diagnostic Approach? A Case Report".

Encephalitis related to antibodies against the N-methyl-D-aspartate receptor (NMDAr) is a recently described clinical entity in which IgG autoantibodies against the NR1 subunit of the NMDAr lead to the appearance of complex neuropsychiatric symptoms. As psychiatric symptoms predominate in early stages, anti-NMDAr encephalitis is frequently mistaken as a primary psychiatric disorder which delays treatment and has serious consequences for patients. This report presents the case of a 24-year-old woman with a subacute onset of psychotic and catatonic symptoms in whom current diagnostic criteria for probable anti-NMDAr encephalitis were not fulfilled. On the basis of the red flags that have been proposed to raise suspicion of anti-NMDAr encephalitis, a study of fluorodeoxyglucose positron emission tomography was requested and demonstrated bilateral occipital hypometabolism consistent with clinical suspicion of anti-NMDAr encephalitis. Once the appropriate treatment was established, the patient recovered completely. This case supports the need to maintain clinical suspicion of anti-NMDAr encephalitis, even when conventional diagnostic tests have been normal. Psychiatrists should be familiar with this entity to promote timely diagnosis and prompt treatment.

Commentary on "Basal Ganglia Calcification: A Case Report of Fahr Disease With Pure Psychiatric Symptoms".

Fahr disease, also known as familial idiopathic basal ganglia calcification, is a rare neurodegenerative disorder, the etiology of which remains unknown. Given its various presentations, Fahr disease is presumed to be underdiagnosed and its prevalence underestimated. We present a case of Fahr disease that presented mainly with pure psychiatric symptoms. Isolated psychiatric symptoms without neurological manifestations are rarely seen in patients diagnosed with Fahr disease. Psychiatrists should consider Fahr disease as a differential diagnosis in the evaluation of psychiatric illness.

Commentary on "A Call for Caution in Prescribing Gabapentin to Individuals with Concurrent Polysubstance Abuse: A Case Report".

Gabapentin is an anticonvulsant medication with an indication from the US Food and Drug Administration for use in partial onset seizures and postherpetic neuralgia in the United States. Currently, gabapentin is only classified as a controlled substance subject to stricter prescribing and distributing regulations in certain states, as opposed to pregabalin, an anticonvulsant with a similar mechanism of action which is a considered a Schedule V medication under federal law. Gabapentin shares a structural similarity to pregabalin, and several case reports have suggested that gabapentin has a similar propensity for abuse. The mechanisms of the gabapentin reward pathway, addiction, and withdrawal, however, are not well known. This case report describes a patient with long-term polysubstance abuse and new onset gabapentin dependence and demonstrates the need for increased surveillance of gabapentin prescribing.

Commentary: Aripiprazole: The Second Wave of the Second-generation Antipsychotics.

Three cases are presented describing unique clinical responses to aripiprazole in comparison with other second-generation antipsychotics taken by each patient. One case involved an adverse reaction of problem gambling behavior, the second an enhanced antipsychotic response in delusional disorder, and the third a reversal of weight gain that occurred while the patient continued taking olanzapine. Aripiprazole was the first of a subgroup of atypical antipsychotics that are mixed agonists and antagonists of dopamine, likely contributing to unusual responses in some patients.

Is Ketamine the Future Clozapine for Depression? A Case Series and Literature Review on Maintenance Ketamine in Treatment-resistant Depression With Suicidal Behavior.

Ketamine has shown effectiveness as a rapid-acting antidepressant with antisuicidal effects in terms of reduction of suicidal ideation in the short term. However, the evidence for long-term maintenance ketamine therapy for treatment-resistant depression (TRD) and suicidal behavior is limited. This case series (N=13) highlights the role of adjunctive serial maintenance ketamine infusions in restoring functionality in treatment-resistant unipolar and bipolar (mixed) depression with significant suicide risk and multiple comorbidities, including alcohol dependence. Two cases of TRD achieved functional remission with long-term maintenance ketamine treatment. The first case illustrates the potential synergistic interaction between ketamine and lamotrigine to achieve a sustained antidepressant response in the patient for 7 months. The second case may possibly be the longest reported case of maintenance ketamine therapy, with treatment continuing for 5 years to date. Ketamine treatment showed acute effectiveness in another 7 cases, especially in terms of reduction of suicidal ideation, albeit without significant long-term antidepressant effect. Factors that may contribute to lack of effectiveness of serial ketamine include inadequate mood stabilization in TRD in bipolar spectrum diagnoses, concomitant benzodiazepine use, complex comorbidities, and adverse effects such as significant hypertension and severe dissociation. Future systematic controlled studies are warranted to establish the efficacy and safety profile of long-term ketamine as maintenance therapy for TRD with suicidal behavior.

Commentary: Role of the Endogenous Opiate System in Psychiatric Disorders Other Than Addiction.

Two case reports explore opiate use in relation to 2 different psychiatric disorders. In the first case report, the authors reported the finding that opiate abuse appeared to mitigate premorbid Tourette syndrome in a small series of patients with opiate addiction and that this benefit was maintained with medically supervised opiate agonist therapy. In the second case report, the authors noted a significant correlation between prescription opiate use and delusions of infestation in a large psychodermatology clinic (as well as a separate, stronger correlation with stimulant use). These reports highlight the importance of the opiate system in a range of psychiatric disorders, suggesting that there is much more to learn about the role of the endogenous opiate system in brain functioning, and its potential as a target for therapeutic intervention in psychiatric disorders other than addiction.

Brain and Behavior: Commentary on Two Cases Involving the Effect of Structural Brain Lesions on Psychiatric Disorders.

In this issue of the journal, 2 case reports are presented that illustrate explicit influences of structural brain lesions on psychiatric symptoms. In both cases, the patients had preexisting, classically diagnosed psychiatric disorders-schizophrenia in the first case and bipolar I disorder in the second case. In the first case, a 61-year-old woman with chronic paranoid schizophrenia experienced a marked reduction in psychotic symptoms after bilateral frontal strokes. In the second case, a 60-year-old man who had experienced manic and depressive episodes since his 20s developed partial complex seizures after having repeated head trauma in his 40s, with subsequent onset of chronic personality changes associated with temporal lobe epilepsy that made his psychiatric treatment a greater challenge. The presentations in these 2 cases raise intriguing neuropsychiatric questions concerning the effects on regional brain activity of a variety of nonpharmacological psychiatric interventions (eg, stereotactic neurosurgical techniques, deep brain stimulation, electroconvulsive therapy, certain types of psychotherapy), and concerning possible physiological pathways shared by seizure kindling in epilepsy and recurrent episodes of bipolar disorder.

Commentary on 2 Cases of Rare but Serious Side Effects of Commonly Used Medications: Dilemmas in Clinical Decision-making.

In this issue of the journal, 2 case reports are presented that describe rare but serious side effects of commonly used medications. These cases illustrate dilemmas in clinical decision-making. The first describes the induction of seizures by low-dose venlafaxine in a predisposed individual, and the second describes the development of mild but significant leukopenia with sequential trials of olanzapine and risperidone. The association between a drug and a rare but potentially serious side effect in an individual patient can be difficult to determine with precision, and the decision to press ahead and try to work around the reaction, versus stopping the likely offender and finding a substitute, is a matter for seasoned clinical judgment.

Clozapine Treatment of Olanzapine-induced Tardive Dyskinesia: A Case Report.

Tardive dyskinesias (TD) are serious, often irreversible side effects of dopamine blocking agents, most commonly first-generation antipsychotics. No definitive treatment exists, with different interventions showing inconsistent results. We report a case of TD presenting after 12 years of olanzapine therapy in a 66-year-old Hispanic male with paranoid schizophrenia. The TD symptoms were successfully treated within a few weeks by switching to clozapine. Two cases of olanzapine-induced TD treated with clozapine have previously been reported, but in those cases, the symptom onset was quicker, ranging from a few months to a few years after initiation of olanzapine therapy, and the treatment response was relatively slower. Clinicians should carefully monitor for symptoms of TD after prolonged treatment with olanzapine and other antipsychotics. If otherwise indicated for psychiatric treatment, clozapine can be considered a good choice for patients with TD in preventing or reversing the debilitating consequences of this condition.

Voltage-gated Potassium Channel Antibody Autoimmune Encephalopathy Presenting With Isolated Psychosis in an Adolescent.

Antibody-mediated encephalopathies associated with serum or cerebrospinal fluid antibodies directed against neuronal structures may present with a multitude of neuropsychiatric syndromes. Although some of the antibody-driven conditions are now well recognized in adults (eg, N-methyl-D-aspartate receptor antibody encephalitis), the spectrum of neuropsychiatric manifestations in the pediatric population is less clear. Psychosis, confusion, catatonia, and additional behavioral changes, along with seizures, encephalopathy, and movement disorders, may be initial manifestations or concurrent features in all age groups. Psychosis, when present, is often part of a broader spectrum of neurological and neuropsychiatric symptoms for which the diagnosis of autoimmune encephalitis is considered. The authors present the case of an adolescent with an acute and isolated psychotic presentation of voltage-gated potassium channel antibody encephalitis, further expanding the phenotypic spectrum of this specific antibody-mediated disease and raising the possibility that specific immune-mediated processes may define a biological subgroup of psychoses.

Reward Dysfunction in the Manic Spectrum: Unable to Win? The Use of Biographical Information to Refine Neurobiological Modeling.

OBJECTIVE: The manic spectrum is thought to be characterized by a hypersensitive biobehavioral reward system, the behavioral activation system. Evidence for this framework comes from questionnaire-based, self-report data collected in cross-sectional and prospective studies of mania, mania in remission, and proneness to hypomania, and from functional neuroimaging investigations of brain reward circuit activity during incentivized choice protocols. Although heightened reward anticipation is consistently documented, the status of later goal attainment activity, hedonic responses, and satiety reactions is less clear. This report examines the status of such reward receipt processes as they operate in the manic spectrum. METHODS: A case report of a typical subject with bipolar II disorder with a hyperthymic temperament is presented using longitudinal, biographical data. RESULTS: Diminished reward receipt, pleasure, and satiety were demonstrated indicating impaired hedonic processing in hyperthymic temperament. This impairment indicates a dissociation between early, intensified reward pursuit processes and later, blunted, reward attainment activity. CONCLUSIONS: The experience and neural correlates of hedonic processing may be impaired in the manic spectrum. Possible mechanisms for this impairment and its dissociation from the earlier stage of reward processing characterized by hyperactive reward pursuit are considered. Clinical reports and longitudinal, life-based follow-up can provide important data to supplement more experimentally based neurobiological models of reward dysfunction in bipolar disorders.

Commentary on 3 Unusual Cases Involving Electroconvulsive Therapy.

Well-established practice guidelines and a solid body of evidence underpin the safe and effective use of electroconvulsive therapy (ECT), primarily in mood disorders. In this issue of the journal, 3 case reports deal with situations that fall outside of the usual guidelines: treatment resistance to ECT overcome by combined use with antidepressant medication; use of ECT in the presence of polymyositis; and use of ECT for an unusually severe case of neuroleptic malignant syndrome, assisted by consultation from an online expert resource. The value of case reports and expert consultation in situations in which there is little or no evidence from clinical trials is also discussed.

Pyrotherapy for the Treatment of Psychosis in the 21st Century: A Case Report and Literature Review.

The concept that fevers can improve the condition of patients with certain medical and psychiatric diseases dates back to Hippocrates. Over the centuries, it has been observed that fevers and infectious agents have been beneficial for a broad spectrum of diseases, including neurologic conditions such as epilepsy and psychiatric illnesses including melancholy and psychosis. Interest in the concept of fever as a treatment for disease, termed pyrotherapy or pyretotherapy, peaked in the late 1800s and early 1900s thanks to the Nobel Prize winning work of Julius Wagner-Jauregg for his studies with malaria therapy for general paralysis of the insane, now more commonly referred to as neurosyphilis. The use of inoculations of infectious agents for their fever-inducing effects in the treatment of neurosyphilis quickly spread throughout the world, and, by the 1920s, it was considered by many to be the treatment of choice for neurosyphilis as well as other psychotic disorders. However, with the discovery of penicillin for the treatment of syphilis, which coincided with the advent of convulsion-oriented practices including electroconvulsive therapy and insulin coma for the treatment of psychotic disorders, pyrotherapy soon lost favor among psychiatrists and, since the 1950s, it has largely been overlooked by the scientific community. In this article, the authors provide a brief literature review of the history of pyrotherapy and present a case report of a woman with schizoaffective disorder and severe psychotic symptoms who experienced a remarkable resolution of psychotic symptoms following an episode of bacteremia with high fever.

Commentary on 2 Unusual Cases.

Two cases of unusual situations are discussed: one involving feigned suicide detected as false only after a comparison of surveillance systems, and one involving monozygotic triplets who all developed psychosis with shared delusions. Although these 2 cases involve presentations most of us will never encounter as clinicians, they nevertheless serve to highlight fundamental questions about the nature of psychopathology. Both cases also have compelling parallels in literature and film.

Varying Timescales of Stimulus Integration Unite Neural Adaptation and Prototype Formation.

Human visual perception is both stable and adaptive. Perception of complex objects, such as faces, is shaped by the long-term average of experience as well as immediate, comparative context. Measurements of brain activity have demonstrated corresponding neural mechanisms, including norm-based responses reflective of stored prototype representations, and adaptation induced by the immediately preceding stimulus. Here, we consider the possibility that these apparently separate phenomena can arise from a single mechanism of sensory integration operating over varying timescales. We used fMRI to measure neural responses from the fusiform gyrus while subjects observed a rapid stream of face stimuli. Neural activity at this cortical site was best explained by the integration of sensory experience over multiple sequential stimuli, following a decaying-exponential weighting function. Although this neural activity could be mistaken for immediate neural adaptation or long-term, norm-based responses, it in fact reflected a timescale of integration intermediate to both. We then examined the timescale of sensory integration across the cortex. We found a gradient that ranged from rapid sensory integration in early visual areas, to long-term, stable representations in higher-level, ventral-temporal cortex. These findings were replicated with a new set of face stimuli and subjects. Our results suggest that a cascade of visual areas integrate sensory experience, transforming highly adaptable responses at early stages to stable representations at higher levels.

Commentary on 2 Cases Involving Psychiatric Problems Following Organ Transplantation.

Organ transplantation may be complicated by a range of psychiatric difficulties. We present 1 case reporting that tacrolimus-induced catatonic delirium after liver transplant responded to memantine, and another case illustrating the need for ongoing psychosocial assessment and support after heart transplant.