Guillermo Horga
Columbia University, Psychiatry, Faculty Member
Research Interests:
Research Interests:
The processing of cognitive interference is a self-regulatory capacity that is impaired in persons with internalizing disorders. This investigation was to assess sex differences in the neural correlates of cognitive interference in... more
The processing of cognitive interference is a self-regulatory capacity that is impaired in persons with internalizing disorders. This investigation was to assess sex differences in the neural correlates of cognitive interference in individuals with and without an illness history of an internalizing disorder. We compared functional magnetic resonance imaging blood-oxygenation-level-dependent responses in both males (n=63) and females (n=80) with and without this illness history during performance of the Simon task. Females deactivated superior frontal gyrus, inferior parietal lobe, and posterior cingulate cortex to a greater extent than males. Females with a prior history of internalizing disorder also deactivated these regions more compared to males with that history, and they additionally demonstrated greater activation of right inferior frontal gyrus. These group differences were represented in a significant sex-by-illness interaction in these regions. These deactivated regions compose a task-negative or default mode network, whereas the inferior frontal gyrus usually activates when performing an attention-demanding task and is a key component of a task-positive network. Our findings suggest that a prior history of internalizing disorders disproportionately influences functioning of the default mode network and is associated with an accompanying activation of the task-positive network in females during the resolution of cognitive interference.
Research Interests:
Electroconvulsive therapy is scarcely used in adolescents with diagnoses of schizophrenia, although it has been reported as an effective and safe treatment in the previous literature. We present 3 cases of early adolescent patients with... more
Electroconvulsive therapy is scarcely used in adolescents with diagnoses of schizophrenia, although it has been reported as an effective and safe treatment in the previous literature. We present 3 cases of early adolescent patients with schizophrenia who were treated with electroconvulsive therapy without adverse effects.
Research Interests:
Research Interests: Schizophrenia, Magnetic Resonance Imaging, Brain Mapping, Humans, Outcome, and 13 moreCerebral Cortex, Female, Male, Magnetic Resonance, Longitudinal Studies, Family Health, Disease Progression, Psychotic Disorders, Healthy Subjects, Gray Matter, Functional Laterality, Psychiatric Status Rating Scales, and Neuropsychological Tests
Cognitive control, a set of functions that develop throughout adolescence, is important in the pathogenesis of psychotic disorders. Whether cognitive control pays a role in conferring vulnerability for the development of psychotic illness... more
Cognitive control, a set of functions that develop throughout adolescence, is important in the pathogenesis of psychotic disorders. Whether cognitive control pays a role in conferring vulnerability for the development of psychotic illness is still unknown. The aim of this study was to investigate the neural systems supporting cognitive control in individuals deemed to be potentially prodromal for psychotic illness. We recruited 56 participants at clinical high-risk (CHR) for psychosis based on the Structured Interview for Psychosis-Risk Syndromes (SIPS) and 49 healthy controls. Twelve of the CHR participants eventually developed psychosis. We compared functional magnetic resonance imaging (fMRI) BOLD signal during the performance of the Simon task. We tested for differences between CHR individuals and controls in conflict-related functional activity. In the CHR group when compared to controls, we detected smaller conflict-related activations in several cortical areas, including the Dorsolateral Prefrontal Cortex (DLPFC). Furthermore, conflict-related activations in the DLPFC of those CHR individuals who ultimately developed psychosis (CHR converters) were smaller than in non-converters (CHR-non converters). Higher levels of conflict-related activation were associated with better social and role outcome. Risk for psychosis was associated at the neural level with reduced conflict-related brain activity. This neural phenotype appears correlated within the DLPFC with the development of psychosis and functional outcome.Neuropsychopharmacology accepted article preview online, 10 September 2015. doi:10.1038/npp.2015.273.
Research Interests:
Research Interests: Cognitive Science, Psychophysics, Algorithms, Reinforcement Learning, Magnetic Resonance Imaging, and 14 moreBrain Mapping, Humans, Hemodynamics, Female, Male, Computer User Interface Design, Adult, Human Brain Mapping, Neural pathways, Putamen, Maze Learning, Neurosciences, Choice Behavior, and Neuropsychological Tests
The neural mechanisms that produce hallucinations and other psychotic symptoms remain unclear. Previous research suggests that deficits in predictive signals for learning, such as prediction error signals, may underlie psychotic symptoms,... more
The neural mechanisms that produce hallucinations and other psychotic symptoms remain unclear. Previous research suggests that deficits in predictive signals for learning, such as prediction error signals, may underlie psychotic symptoms, but the mechanism by which such deficits produce psychotic symptoms remains to be established. We used model-based fMRI to study sensory prediction errors in human patients with schizophrenia who report daily auditory verbal hallucinations (AVHs) and sociodemographically matched healthy control subjects. We manipulated participants' expectations for hearing speech at different periods within a speech decision-making task. Patients activated a voice-sensitive region of the auditory cortex while they experienced AVHs in the scanner and displayed a concomitant deficit in prediction error signals in a similar portion of auditory cortex. This prediction error deficit correlated strongly with increased activity during silence and with reduced volumes of the auditory cortex, two established neural phenotypes of AVHs. Furthermore, patients with more severe AVHs had more deficient prediction error signals and greater activity during silence within the region of auditory cortex where groups differed, regardless of the severity of psychotic symptoms other than AVHs. Our findings suggest that deficient predictive coding accounts for the resting hyperactivity in sensory cortex that leads to hallucinations.
Research Interests:
Electroconvulsive therapy is scarcely used in adolescents with diagnoses of schizophrenia, although it has been reported as an effective and safe treatment in the previous literature. We present 3 cases of early adolescent patients with... more
Electroconvulsive therapy is scarcely used in adolescents with diagnoses of schizophrenia, although it has been reported as an effective and safe treatment in the previous literature. We present 3 cases of early adolescent patients with schizophrenia who were treated with electroconvulsive therapy without adverse effects.
Research Interests:
Research Interests:
Research Interests: Neuroscience, Magnetic Resonance Imaging, Adolescent, Intergroup Conflict (Psychology), Prefrontal Cortex, and 16 moreBrain Mapping, Humans, Child, Female, Male, Reaction Time, Regression Analysis, Young Adult, The, Mental Disorders, Aged, Middle Aged, Oxygen, Adult, Analysis of Variance, and Time Factors
Research Interests: Schizophrenia, Magnetic Resonance Imaging, Brain Mapping, Humans, Outcome, and 13 moreCerebral Cortex, Female, Male, Magnetic Resonance, Longitudinal Studies, Family Health, Disease Progression, Psychotic Disorders, Healthy Subjects, Gray Matter, Functional Laterality, Psychiatric Status Rating Scales, and Neuropsychological Tests
Research Interests:
Research Interests:
Research Interests:
The widespread use of Magnetic Resonance Imaging (MRI) in the study of child- and adult-onset developmental psychopathologies has generated many investigations that have measured brain structure and function in vivo throughout... more
The widespread use of Magnetic Resonance Imaging (MRI) in the study of child- and adult-onset developmental psychopathologies has generated many investigations that have measured brain structure and function in vivo throughout development, often generating great excitement over our ability to visualize the living, developing brain using the attractive, even seductive images that these studies produce. Often lost in this excitement is the recognition that brain imaging generally, and MRI in particular, is simply a technology, one that does not fundamentally differ from any other technology, be it a blood test, a genotyping assay, a biochemical assay, or behavioral test. No technology alone can generate valid scientific findings. Rather, it is only technology coupled with a strong experimental design that can generate valid and reproducible findings that lead to new insights into the mechanisms of disease and therapeutic response. In this review we discuss selected studies to illustrate the most common and important limitations of MRI study designs as most commonly implemented thus far, as well as the misunderstanding that the interpretations of findings from those studies can create for our theories of developmental psychopathologies. Common limitations of MRI study designs are in large part responsible thus far for the generally poor reproducibility of findings across studies, poor generalizability to the larger population, failure to identify developmental trajectories, inability to distinguish causes from effects of illness, and poor ability to infer causal mechanisms in most MRI studies of developmental psychopathologies. For each of these limitations in study design and the difficulties they entail for the interpretation of findings, we discuss various approaches that numerous laboratories are now taking to address those difficulties, which have in common the yoking of brain imaging technologies to studies with inherently stronger designs that permit more valid and more powerful causal inferences. Those study designs include epidemiological, longitudinal, high-risk, clinical trials, and multimodal imaging studies. We highlight several studies that have yoked brain imaging technologies to these stronger designs to illustrate how doing so can aid our understanding of disease mechanisms and in the foreseeable future can improve clinical diagnosis, prevention, and treatment planning for developmental psychopathologies.
Research Interests:
Research Interests:
Research Interests: Cognitive Science, Schizophrenia, Nuclear medicine, Face recognition (Psychology), Facial expression, and 17 morePositron Emission Tomography, Emotions, Brain Mapping, Humans, Emotion Recognition, Male, Reaction Time, Young Adult, Amygdala, Clinical Sciences, Adult, Hemispheric Specialization, Limbic System, Healthy Subjects, Neurosciences, Right Handed, and Region of Interest
Ziprasidone was the fifth atypical antipsychotic approved by Food and Drug Administration (FDA) for use in bipolar mania and mixed episodes. This atypical antipsychotic has a unique profile, as it acts primarily through serotonergic and... more
Ziprasidone was the fifth atypical antipsychotic approved by Food and Drug Administration (FDA) for use in bipolar mania and mixed episodes. This atypical antipsychotic has a unique profile, as it acts primarily through serotonergic and dopaminergic receptor antagonism, but also exerts effects as an inhibitor of norepinephrine reuptake. Moreover, one of the advantages of ziprasidone is its safety profile as it is not associated with clinically significant metabolic side effects and little or no effect on prolactin level or anticholinergic side effects. Most of the studies evaluating ziprasidone's efficacy and safety are short-term double-blind, placebo-controlled studies in acute mania and mixed episodes. In two of them, ziprasidone was associated to significant improvement in the primary measures assessed. However, an add-on study, lithium plus ziprasidone showed similar results than lithium monotherapy, although there was a significant advantage for the combination within the first week. In a more recent trial, ziprasidone was compared with placebo and haloperidol as monotherapies, again beating placebo. In that trial, ziprasidone appeared to be safer and better tolerated, although less likely efficacious than haloperidol. Particularly, subjects treated with ziprasidone were less likely to switch to depression. Despite the well-studied efficacy of ziprasidone in the first weeks of treatment, there are no controlled trials that evaluate the role and efficacy of ziprasidone in long-term treatment of bipolar disorder (BD). Overall, in the open-label extension studies, there was a global improvement at all visits compared with baseline scores. Furthermore, ziprasidone appears to offer some antidepressant effect in patients with major depressive episode and resistant to treatment, as demonstrated in add-on open-label studies with ziprasidone plus selective serotonin reuptake inhibitor (SSRI).
Research Interests:
The aim of this study was to examine the functioning of fronto-striatal brain circuits that support self-regulatory capacities including conflict resolution and sequential processing in unmedicated adults with obsessive-compulsive... more
The aim of this study was to examine the functioning of fronto-striatal brain circuits that support self-regulatory capacities including conflict resolution and sequential processing in unmedicated adults with obsessive-compulsive disorder (OCD). We compared functional magnetic resonance imaging blood oxygen level-dependent response in 22 adults with OCD with 22 healthy, age-matched control subjects during performance of a Simon Spatial Incompatibility task. We used general linear modeling to compare groups in their patterns of brain activation during correct responses to conflict-laden stimuli and explore the effects of trial sequence on group differences. Behavioral performance on the Simon task did not differ between groups. In response to conflict-laden stimuli, OCD participants activated fronto-striatal regions significantly more than control subjects, specifically a right hemisphere cluster encompassing the putamen, insula, and inferior frontal gyrus. Their activation of this cluster was driven not by conflict on a current trial but by their response to the alternation of stimulus congruence (incongruent or congruent) across trial sequences (i.e., current and preceding trials) and was most accentuated in participants with more severe symptoms in the doubt/checking dimension. Functional connectivity from the putamen to other fronto-striatal regions was also greater in the OCD compared with control participants. When engaging the self-regulatory control necessary to resolve conflict and process alternating stimuli, OCD participants displayed excessive activation in a fronto-striatal circuit that differs from the orbitofrontal cortex-anterior cingulate cortex-caudate circuit typically implicated in OCD. Dysfunction in this circuit was associated with processing changes in the stimulus context. We speculate that this dysfunction might be related to the cognitive inflexibility typical of persons with OCD.