Michael Minzenberg

University of California, Los Angeles | UCLA · Department of Psychiatry and Biobehavioural Sciences

Excess synaptic pruning during neurodevelopment has emerged as one of the leading hypotheses on the causal mechanism for schizophrenia. It proposes that excess synaptic elimination occurs during development before the formal onset of illness. Accordingly, synaptic deficits may be observable at all stages of illnesses, including in the early phases....

Introduction Conspiratorial beliefs are often maladaptive for individuals and dangerous for societies. Other prevalent belief systems such as (normative) religious belief and (pathological) delusional belief show parallels to conspiratorial beliefs, which may also be linked to excessive social media exposure. We conducted an online survey to charac...

Blunted and exaggerated neuronal response to rewards are hypothesized to be core features of schizophrenia spectrum disorders (SZ) and bipolar disorder (BD), respectively. Nonetheless, direct tests of this hypothesis, in which response between SZ and BD is compared in the same study, are lacking. Here we examined the functional correlates of reward...

Transcranial magnetic stimulation (TMS) is a safe and effective therapeutic modality for a rapidly expanding range of neuropsychiatric indications. Among psychiatric conditions, it is presently approved by the US Food and Drug Administration for treatment-resistant unipolar major depressive disorder and obsessive-compulsive disorder, 2 highly preva...

Repetitive transcranial magnetic stimulation (rTMS) treatment of major depressive disorder (MDD) is associated with changes in brain functional connectivity (FC). These changes may be related to the mechanism of action of rTMS and explain the variability in clinical outcome. We examined changes in electroencephalographic FC during the first rTMS tr...

The GABA deficit hypothesis remains one of the most compelling explanations for the information processing impairments in schizophrenia. However, much of the supportive evidence has been derived from post-mortem studies, whereas in vivo studies have largely yielded inconsistent results. We undertook this single voxel proton magnetic resonance (MRS)...

Background: The therapeutic mechanism of repetitive transcranial magnetic stimulation (rTMS) for treatment-resistant depression (TRD) may involve modulation of γ-aminobutyric acid (GABA) levels. We used proton magnetic resonance spectroscopy (MRS) to assess changes in GABA levels at the site of rTMS in the left dorsolateral prefrontal cortex (DLPF...

Background Repetitive Transcranial Magnetic Stimulation (rTMS) is commonly administered to Major Depressive Disorder (MDD) patients taking psychotropic medications, yet the effects on treatment outcomes remain unknown. We explored how concomitant medication use relates to clinical response to a standard course of rTMS. Methods Medications were tab...

Working memory (WM) deficits are key features of schizophrenia and are associated with significant functional impairment. The precise mechanisms of WM and their relationship between WM deficits with other clinical symptoms of schizophrenia remain unclear. Contemporary models propose that WM requires synchronous activity across brain regions within...

The subthalamic nucleus (STN) is thought to be a central regulator of behavioral inhibition, which is thought to be a major determinant of impulsivity. Thus, it would be reasonable to hypothesize that STN function is related to impulsivity. However, it has been difficult to test this hypothesis because of the challenges in noninvasively and accurat...

Candidate pro-cognitive drugs for schizophrenia targeting several neurochemical systems have consistently failed to demonstrate robust efficacy. It remains untested whether concurrent antipsychotic medications exert pharmacodynamic interactions that mitigate pro-cognitive action in patients. We used functional MRI (fMRI) in a randomized, double-bli...

Repetitive transcranial magnetic stimulation (rTMS) has demonstrated efficacy in major depressive disorder (MDD), although clinical outcome is variable. Change in the resting-state quantitative electroencephalogram (qEEG), particularly in theta cordance early in the course of treatment, has been linked to antidepressant medication outcomes but has...

The borderline construct has remained enigmatic across generations of clinicians and research traditions since its first appearance in psychiatric literature in the 20th century.¹ This construct has traveled from early conceptions of the individual on the “border” of neurosis and psychosis to its current home in a DSM cluster of personality disorde...

Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for Major Depressive Disorder (MDD). There are clinical data that support the efficacy of many different approaches to rTMS treatment, and it remains unclear what combination of stimulation parameters is optimal to relieve depressive symptoms. Because of the costs and com...

Suicidal ideation and behavior are highly prevalent in psychotic major mood disorders, yet their relationship to brain function remains unclear. Thirty patients with recent-onset of bipolar disorder type I (N=21) or major depressive disorder (N=9) with past psychosis were evaluated for past suicidal ideation/behavior and functional MRI during confl...

Objective: Suicide is highly-prevalent in major mood disorders, yet it remains unclear how suicidal ideation and suicidal behavior relate to brain functions, especially those that support control processes. We evaluated how prefrontal cortex (PFC) activity during goal-representation (an important component of cognitive control) relates to past sui...

Control-related cognitive processes such as rule-selection and maintenance are associated with cortical oscillations in the gamma range, and modulated by catecholamine neurotransmission. Control-related gamma power is impaired in schizophrenia, and an understudied treatment target. It remains unknown whether pro-catecholamine pharmacological agents...

Background: Suicide is prevalent in schizophrenia (SZ), yet the neural system functions that confer suicide risk remain obscure. Circuits operated by the prefrontal cortex (PFC) are altered in SZ, including those that support reactive control, and PFC changes are observed in postmortem studies of heterogeneous suicide victims. Aims: We tested wh...

Pupil diameter has long been used as a metric of cognitive processing. However, recent advances suggest that the cognitive sources of change in pupil size may reflect LC-NE function and the calculation of unexpected uncertainty in decision processes (Aston-Jones and Cohen, 2005; Yu and Dayan, 2005). In the current experiments, we explored the role...

Recent data suggest that treatment with antipsychotics is associated with reductions in cortical gray matter in patients with schizophrenia. These findings have led to concerns about the effect of antipsychotic treatment on brain structure and function; however, no studies to date have measured cortical function directly in individuals with schizop...

Impaired functional connectivity has been hypothesized as a potential source of the cognitive deficits routinely observed in patients with schizophrenia. Additionally, these deficits may be manifestations of the genetic liability to schizophrenia and present in the non-psychotic first-degree relatives of that group. However, no study has examined t...

The ability to proactively control motor responses, particularly to overcome overlearned or automatic actions, is an essential prerequisite for adaptive, goal-oriented behavior. The substantia nigra (SN), an element of the BG, has figured prominently in current models of response selection. However, because of its small size and proximity to functi...

Schizophrenia patients experience cognitive control disturbances, manifest in altered neural signatures during action monitoring. It remains unclear whether error- and conflict-monitoring disturbances co-occur, and whether they are observed in recent-onset psychosis patients with schizophrenia or bipolar disorder. We tested electrophysiological mea...

The majority of studies examining self-reported anticipatory and consummatory pleasure in schizophrenia, as measured on the Temporal Experience of Pleasure Scale (TEPS), have been conducted on chronically ill people with the disorder. In this study, people with a recent-onset schizophrenia spectrum diagnosis (first psychotic episode within one year...

Control-related cognitive processes such as rule-selection are associated with cortical oscillations in the theta, alpha and beta ranges, and modulated by catecholamine neurotransmission. Thus, a potential strategy for improving cognitive control deficits in schizophrenia would be to use pro-catecholamine pharmacological agents to augment these con...

Child abuse can negatively affect neurobiological systems involved in regulating emotions. Adults who were maltreated as children show diminished capacity to flexibly integrate the prefrontal and limbic circuits underlying emotion regulation. Using a facial identification Stroop task with nonemotional and emotional stimuli, we found that women who...

Control-related cognitive processes are associated with cortical oscillations and modulated by catecholamine neurotransmitters. It remains unclear how catecholamine systems modulate control-related oscillations. We tested modafinil effects on rule-related 4-30 Hz oscillations, with double-blind, placebo-controlled (within-subjects) testing of 22 he...

While structural abnormalities of the dorsolateral prefrontal cortex (DLPFC) may pre-date and predict psychosis onset, the relationships between functional deficits, cognitive and psychosocial impairments has yet to be explored in the at-risk period. An established measure of cognitive control (AXCPT) was administered to demographically matched cli...

Cognitive control deficits have been consistently documented in patients with schizophrenia. Recent work in cognitive neuroscience has hypothesized a distinction between two theoretically separable modes of cognitive control-reactive and proactive. However, it remains unclear the extent to which these processes are uniquely associated with dysfunct...

Background: The theory that prefrontal cortex (PFC) dysfunction in schizophrenia leads to excess subcortical dopamine has generated widespread interest because it provides a parsimonious account for two core features of schizophrenia, cognitive deficits and psychosis, respectively. However, there has been limited empirical validation of this model...

When predicting where a target or reward will be, subjects tend to choose each location commensurate with the true underlying probability (i.e., to probability match). The strategy of probability matching includes sampling high and low probability locations on some proportion of trials. In contrast, models of probabilistic spatial attention hypothe...

Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent disorder of childhood and adulthood, with a considerable impact on public health. There is a substantial pharmacopoeia available for safe and effective treatment of ADHD, and newly available agents diversify the treatment options. With the burgeoning scientific literature address...

Schizophrenia is characterized by significant problems in control of behavior; however, the disturbances in neural systems that control movement remain poorly characterized. We used functional magnetic resonance imaging (fMRI) to evaluate the origin of motor overflow in schizophrenia. Twenty-seven clinically stable medicated outpatients with Diagno...

The establishment of a neurobiologically based nosological system is one of the ultimate goals of modern biological psychiatry research. Developments in neuroimaging and statistical/machine learning have provided useful basic tools for these efforts. Recent studies have demonstrated the utility of fMRI as input data for the classification of schizo...

Schizophrenia is one of the most debilitating of all common brain disorders, exacting a heavy toll on the afflicted and having a tremendous public health impact. Clinical outcome is more strongly predicted by cognitive deficits than psychotic symptoms, with no established treatment for these deficits. In this review, we discuss the status of treatm...

In this article, we describe results of the 5th Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia meeting which identified candidate imaging biomarkers for used in measuring neural activity associated with specific component processes of cognition that are targeted for treatment development in schizophrenia and other d...

Functional neuroimaging is a novel technique for the study of drug action in the brain. The emerging role of this method is intimately tied to the unique challenges to advancing drug development for neuropsychiatric disorders. This chapter first presents a brief overview of the important treatment needs that remain to be met, which serve as clinica...

Reduced gamma-aminobutyric acid (GABA) levels in cerebral cortex are thought to contribute to information processing deficits in patients with schizophrenia (SZ), and we have previously reported lower in vivo GABA levels in the visual cortex of patients with SZ. GABA-mediated inhibition plays a role in sharpening orientation tuning of visual cortic...

Childhood abuse and neglect can have far-reaching effects on adult relationships, mental health, and parenting. This study examined relations between maltreatment types, anxious and avoidant adult attachment, maternal depression, and parental self-efficacy in a community sample of 76 at-risk mothers. After controlling for other forms of maltreatmen...

Background: Male predominance of autism spectrum disorders (ASD) is estimated at 4 to 1. One theory for this higher male prevalence is that the female neuroendocrine system confers “protection” against autistic traits (Carter, 2007). According to this view, processes mediated by oxytocin (OT), and the lack of reliance on arginine vasopressin (AVP),...

Brain regions with changes in activity associated with task performance. Statistical parametric map of the contrast of event minus baseline, on placebo (p < 0.0005 uncorrected). The DMN is evident with TID in the vmPFC, PCC/rSpl, and bilateral IPL. The task-positive network is observed as positive activations primarily in sensory and motor regions....

Brain regions with augmented task-induced deactivation within the default mode network on modafinil. Statistical parametric map of the contrast of drug minus placebo, restricted to the conjunction of the DMN (defined by voxels with TID on both placebo and drug) conjoined with anatomic masks covering the vmPFC, PCC, or bilateral IPL. Images oriented...

Despite schizophrenia patients' reports of diminished experience of emotion in interviews and self-report measures, their emotional experience in the presence of emotional stimuli and in daily life ("in the moment") appears largely intact. To examine emotion-cognition interactions, the authors tested the hypothesis that schizophrenia patients have...

Individuals with autism and schizophrenia exhibit atypical language and social symptoms. The extent to which these symptoms are evident during development and in current functioning is unclear. Three groups of patients aged 11-20 diagnosed as clinical-high-risk for psychosis (CHR; n=15), first episode psychosis (FEP; n=16), and autism spectrum diso...

In vivo mouse model yields unique insights into brain responses to stroke.

Antipsychotic medications exert variable and clinically significant levels of antagonism at central α-adrenergic receptors. To evaluate the impact of this activity on both clinical and experimental measures, an index estimating the relative activity of these medications is needed. We comprehensively searched the empirical literature testing in vitr...

After injury in the central nervous system of adult mammals, many of the axons that remain attached to their intact cell bodies degenerate and decrease in calibre. To understand this process better, we have investigated the relationship between axonal loss, cell loss, and the time course of changes in axonal calibre. Optic nerves (ONs) were crushed...

Faltering inhibitory interneurons in the prefrontal cortex lead to chaos in the schizophrenia brain.

Although schizophrenia is an illness that has been historically characterized by the presence of positive symptomatology, decades of research highlight the importance of cognitive deficits in this disorder. This review proposes that the theoretical model of cognitive control, which is based on contemporary cognitive neuroscience, provides a unifyin...

Functional MRI can be used to monitor the action of new drugs in the brains of Parkinson's disease patients.

Although stress is unavoidable in our lives, it can have myriad negative consequences. Some individuals display maladaptive responses to stress that lead to psychiatric disorders, which typically involve dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis—a set of interactions between

Schizophrenia is characterized by impaired cognitive control associated with prefrontal cortex dysfunction, but the underlying pathophysiological mechanisms remain unknown. Higher cognitive processes are associated with cortical oscillations in the gamma range, which are also impaired in chronic schizophrenia. We tested whether cognitive control-re...

The default mode network (DMN) is a functional network which is implicated in a range of cognitive processes. This network is proposed to consist of hubs located in the ventromedial prefrontal cortex (vmPFC), posterior cingulate/retrosplenial cortex (PCC/rSpl), and inferior parietal lobule (IPL), with other midline cortical and temporal lobe nodes...

Patients with HIV enjoy much longer lives now, a benefit of combination antiretroviral therapy. The downside of this longevity is that there is time for various clinical sequelae to emerge. One of these—HIV-associated neurological disease or HAND—confers significant morbidity. HAND often affects

Sharp, sudden pain and dull, aching long-lasting pain: Both arise from myriad underlying conditions and lead to considerable worldwide disability. Although a number of neurotransmitter systems in both the central nervous system and the periphery are known to process pain signals, the relatively

Stroke is a devastating event that has catastrophic consequences for those who survive. Although much is known about risk factors for stroke, there are few options for the long-term care of stroke patients. Recent work has shown that neural circuits in the brain become reorganized after stroke and

Amyotrophic lateral sclerosis (ALS), better known as Lou Gehrig’s disease, is always fatal—usually after years of progressive degeneration of the upper motor neurons of the brain and the lower motor neurons of the spinal cord. A small proportion of individuals with familial (inherited) ALS carry

As common neuropsychiatric disorders with limited treatment options, Alzheimer’s disease and schizophrenia have massive public health implications and take their toll on patients and their caretakers alike. Although the etiologies, ages of onset, and disease courses of these illnesses are clearly

Migraine headaches cause great suffering and disability for those afflicted with this common neurovascular disorder. The aura that typically heralds a migraine attack and is a signature of this illness has been attributed to waves of depression in the spontaneous electrical activity of cortical

Ethanol is the most widely used psychotropic substance in the world, and chronic ethanol abuse leads to harmful changes in virtually every organ system in the body. Notably, this includes the brain, where consumption of alcohol can lead to irreversible changes in cognition, mood, and behavior.

A genetic neurodegenerative disorder that strikes relatively early in life, Huntington's disease (HD) follows an inexorable course that ultimately leads to death for all afflicted individuals. HD arises from an alteration in the huntingtin protein that causes the protein to accumulate and form toxic

Antisocial behavior has existed since humans began living in social groups, and it remains a bane of civilized society. Although this complex phenomenon is clearly sensitive to events in an individual’s environment, exciting recent work has emphasized neurobiological factors that underlie these

Why are some individuals with epilepsy at high risk of sudden death? Lethal cardiac arrhythmias may play a role, but the link between brain and heart in this disorder has remained elusive. A breakthrough was suggested, however, with the recent discovery by Noebels and colleagues that mice bearing a

Contrary to the arguments put forth by Astafiev et al., our new analyses and high-resolution replication show that modulation of brain activity by the cognitive enhancing drug modafinil indeed localizes to the locus coeruleus. The authors’ critical stance regarding blood oxygen level–dependent imaging in the brainstem does not follow from their dat...

Inflammatory neurodegenerative conditions—such as multiple sclerosis, cerebral HIV infection, or stroke—deliver the one-two punch. Not only do these diseases induce nerve cell death, they also block neuron regeneration as a result of the inflammatory environment. With the fairly recent

Much has been published about neuron destruction in Alzheimer’s disease, a self-stealing condition with no cure. The disease pathophysiology implicates a peptide known as amyloid-β (Aβ), which accumulates in the brain and exerts a range of toxic effects on neurons. However, it remains uncertain

Recent years have witnessed an explosion in obesity and obesity-related illness, with particularly ominous numbers among children and adolescents. In response, translational investigators have asked what characteristics within the brain determine whether an individual has an eating pattern that puts

The neural mechanisms underlying cognitive deficits in schizophrenia remain essentially unknown. The GABA hypothesis proposes that reduced neuronal GABA concentration and neurotransmission results in cognitive impairments in schizophrenia. However, few in vivo studies have directly examined this hypothesis. We used magnetic resonance spectroscopy (...

Cannabis is the number one illicit drug of abuse worldwide, with as many as 160 million users annually. Cannabis intoxication impairs cognition; alters attention, memory, and perception; and occasionally even produces psychosis. Although there are several valid clinical applications for this

The stress-response system of infant rat brains disrupts the rats' capacity for learning to maintain close proximity to mothers who are stressed themselves.