Biomedical subjects

Martin P Paulus

Publications and source records attributed to Martin P Paulus.

At least 19 recordsLinked to original sources

PubMed2026

Targeting cortico-striatal-amygdalar networks via theta-band frontoparietal synchronization in opioid use disorder: a randomized tACS-fMRI Trial.

Theta-band oscillation is integral to fronto-parietal connectivity in the executive control network and its top-down regulation on subcortical areas. External frontoparietal synchronization using theta-frequency transcranial alternating current (tACS) is a technology to potentially engage this network. In this pre-registered, triple-blind, sham-controlled trial (NCT03907644), we tested this intervention targeting the right frontoparietal network in people with opioid use disorder (OUD) to measure network engagement and behavioral outcomes. Sixty male participants with OUD were randomized to receive 20 min of active or sham 6 Hz tACS (HD electrodes over F4 and P4). Structural, resting-state, task-based fMRI drug cue reactivity, and repeated cue-induced craving assessments were collected immediately before and after stimulation. Pre-registered outcome measures were analyzed using time × group interaction models to examine (1) modulation of drug cue-related brain activity, (2) changes in craving, (3) alterations in functional connectivity, and (4) relationship between electric field, neural responses, and craving behavior. (1) A significant Time × Group interaction revealed decreased post-stimulation opioid cue-related activity in the active group relative to sham, involving key nodes in reward processing (ventral striatum, amygdala and ventral tegmental area) (FWE corrected α = 0.05) (2) subjective craving did not differ significantly between groups (3) Group by time generalized psychophysiological interaction analyses showed increased right frontoparietal network engagement (β = 2.63, p= 0.0308) following stimulation, and increased top-down inhibitory regulation of frontoparietal network on right ventral striatum (β = 1.99, p= 0.037) and left medial amygdala (β = 1.97, p= 0.039) (4) Electric field strength in the right frontal/parietal node predicted frontoparietal network engagement in the active group (r = 0.43, p= 0.02). Together, these findings demonstrate that theta-band frontoparietal tACS can modulate activity and task-dependent coupling within cortical-subcortical circuits in OUD, supporting network-targeted neuromodulation as a potential intervention for addiction.

Humans↗

PubMed2007

Time and decision making: differential contribution of the posterior insular cortex and the striatum during a delay discounting task.

Delay discounting refers to the fact that an immediate reward is valued more than the same reward if it occurs some time in the future. To examine the neural substrates underlying this process, we studied 13 healthy volunteers who repeatedly had to decide between an immediate and parametrically varied delayed hypothetical reward using a delay discounting task during event-related functional magnetic resonance imaging. Subject's preference judgments resulted in different discounting slopes for shorter (<1 year) and for longer (> or =1 year) delays. Neural activation associated with the shorter delays relative to the longer delays was associated with increased activation in the head of the left caudate nucleus and putamen. When individuals selected the delayed relative to the immediate reward, a strong activation was found in bilateral posterior insular cortex. Several brain areas including the left caudate nucleus showed a correlation between the behaviorally determined discounting and brain activation for the contrast of intervals with delays <1 and > or =1 year. These results suggest that (1) the posterior insula, which is a critical component of the decision-making neural network, is involved in delaying gratification and (2) the degree of neural activation in the striatum, which plays a fundamental role in reward prediction and in time estimation, may code for the time delay.

Adolescent↗

PubMed2006

Time-varying amygdala response to emotional faces in generalized social phobia.

BACKGROUND: Individuals with social phobia (SP) have altered behavioral and neural responses to emotional faces and are hypothesized to have deficits in inhibiting emotion-related amygdala responses. We tested for such amygdala deficits to emotional faces in a sample of individuals with SP. METHOD: We used functional magnetic resonance imaging (fMRI) to examine the neural substrates of emotional face processing in 14 generalized SP (gSP) and 14 healthy comparison (HC) participants. Analyses focused on the temporal dynamics of the amygdala, prefrontal cortex (PFC), and fusiform face area (FFA) across blocks of neutral, fear, contempt, anger, and happy faces in gSP versus HC participants. RESULTS: Amygdala responses in participants with gSP occurred later than the HC participants to fear, angry, and happy faces. Parallel PFC responses were found for happy and fear faces. There were no group differences in temporal response patterns in the FFA. CONCLUSIONS: This finding might reflect a neural correlate of atypical orienting responses among individuals with gSP. Commonly reported SP deficits in habituation might reflect neural regions associated with emotional self-evaluations rather than the amygdala. This study highlights the importance of considering time-varying modulation when examining emotion-related processing in individuals with gSP.

Adult↗

PubMed2006

Striatal function in generalized social phobia: a functional magnetic resonance imaging study.

BACKGROUND: Although evidence suggests the involvement of the amygdala in generalized social phobia (GSP), few studies have examined other neural regions. Clinical, preclinical, and dopamine receptor imaging studies demonstrating altered dopaminergic functioning in GSP suggest an association with striatal dysfunction. This is the first functional magnetic resonance imaging (fMRI) study to use a cognitive task known to involve the striatum to examine the neural correlates of GSP. We examined whether subjects with GSP had differential activation in striatal regions compared with healthy control subjects while engaged in a cognitive task that has been shown to activate striatal regions reliably. METHODS: Ten adult, unmedicated subjects with a primary DSM-IV diagnosis of GSP and 10 age-, gender-, and education-matched healthy comparison subjects underwent fMRI while performing the implicit sequence learning task. RESULTS: The GSP and healthy comparison subjects did not differ significantly on the behavioral performance of the task. Subjects with GSP, however, had significantly reduced neural activation related to implicit learning compared with healthy comparison subjects in the left caudate head, left inferior parietal lobe, and bilateral insula. CONCLUSIONS: These findings support the hypothesis that GSP is associated with striatal dysfunction and further the neurobiological understanding of this complex anxiety disorder.

Adult↗

PubMed2006

Lorazepam dose-dependently decreases risk-taking related activation in limbic areas.

RATIONALE: Several studies have examined the role of different neurotransmitter systems in modulating risk-taking behavior. OBJECTIVE: This investigation was aimed to determine whether the benzodiazepine lorazepam dose-dependently alters risk-taking behavior and underlying neural substrates. MATERIALS AND METHODS: Fifteen healthy, nonsmoking, individuals (six women, nine men), aged 18-39 years (mean 27.6 +/- 1.4 years) with 12-18 years of education (mean 15.6 +/- 0.3 years) underwent functional magnetic resonance imaging while performing a risk-taking decision-making task. RESULTS: Our results show that lorazepam did not affect risky behavior at 0.25 and 1 mg, but dose-dependently attenuated activation in (a) the amygdala and medial prefrontal cortex during the response selection phase, and in (b) the bilateral insular cortex and amygdala during the outcome (i.e., rewarded or punished) phase. Furthermore, a lorazepam-induced increase in insular cortex activation was associated with less risky responses. CONCLUSIONS: Taken together, our findings support the idea that GABAergic modulation in limbic and paralimbic structures is important during both the response selection and outcome phase of risk-taking decision-making.

Administration, Oral↗

PubMed2006

Young adult stimulant users' increased striatal activation during uncertainty is related to impulsivity.

BACKGROUND: Young adults who use stimulants (e.g., cocaine, amphetamines) are at particular risk of transitioning to dependence. Previously, we demonstrated increased risk-taking in young adults who had used stimulants (Leland, D.S., Paulus, M.P., 2005. Increased risk-taking decision-making but not altered response to punishment in stimulant-using young adults. Drug. Alcohol Depend. 78, 83-90). Since outcome uncertainty is a critical element of risk, we investigated whether such individuals have different neural responses to uncertainty than their stimulant-naive peers. METHOD: Eleven young adults (age 18-25) who had used stimulants were compared with 11 age- and education-matched stimulant-naive controls using functional magnetic resonance imaging and a card prediction task with relatively certain/uncertain outcome conditions. RESULTS: The caudate, an area involved in processing salient events, was among those regions more active in users than controls in response to uncertainty. Personality measures revealed that users were more impulsive than controls, and that neural response to uncertainty in a number of areas, including the thalamus/caudate, was positively correlated with impulsivity. CONCLUSIONS: These results are consistent with the idea that young adults who have used stimulants find uncertainty particularly salient, due in part to preexisting differences in impulsivity, and may be subject to more "action pressure" when making decisions under uncertainty. This neural and personality profile may constitute a marker for increased risk of stimulant use.

Adult↗

PubMed2006

Anticipation of aversive visual stimuli is associated with increased insula activation in anxiety-prone subjects.

BACKGROUND: Anticipation is a critical component of affective processing in general and for anxiety in particular. Prior research suggests that the right insula plays an important role in anticipation of affective processing during aversive images. This study aimed to test the hypothesis that individuals with increased anxiety-related temperamental traits (anxiety-prone [AP]) relative to anxiety-normative (AN) subjects would show an exaggerated insula response during anticipation of an aversive image. METHODS: 16 AP and 16 AN individuals performed a task in the functional magnetic resonance imaging scanner, during which they viewed pictures of spiders and snakes. Subjects were prompted 4-6 sec before the onset of each aversive image. Blood oxygenation level-dependent signal was contrasted during cued anticipation of images versus non-anticipatory task performance as well as viewing images. RESULTS: As hypothesized, AP subjects showed greater response than AN subjects in the bilateral insula during anticipation. In addition, these individuals had lower activity within the superior/medial frontal gyrus. During the image presentation phase, AN subjects showed greater activation than AP subjects in the bilateral temporal lobes and left superior frontal gyrus. Moreover, bilateral temporal lobe activation during image presentation was inversely correlated with bilateral insula activation during anticipation both within groups and in the combined group. CONCLUSIONS: These data suggest that greater activation of the insula during visual anticipation is associated with visual processing of aversive stimuli in AP individuals. Insula hyperactivity might be a common feature in persons with elevated trait anxiety and, as such, might be a neuroimaging marker for anxiety proneness.

Adolescent↗

PubMed2006

Individuals with schizophrenia present hypo- and hyperactivation during implicit cueing in an inhibitory task.

BACKGROUND: The primary purpose of this investigation was to assess the neural correlates of implicit cueing during an inhibitory task in schizophrenia when performance accuracy was matched with healthy comparison subjects. METHODS: We compared 17 individuals with chronic schizophrenia (SZ; medicated, 13.9 average years of illness) and 17 healthy comparison subjects (HC) matched for hit and false alarm rates, age, and education on a visual Go/Nogo task during functional magnetic resonance imaging. In this task, one of the go stimuli also served implicitly as a cue predictive of a subsequent inhibitory (Nogo) trial. CONCLUSIONS: Findings suggest that even when matched for overall performance accuracy, individuals with SZ exhibit difficulties with inhibition and cue processing that may relate to core deficits in cognitive control and stimulus processing. In particular, these findings point towards an important role of the parietal cortex for cued inhibitory processes in healthy populations.

Adult↗

PubMed2006

Differential contributions of dopamine D1, D2, and D3 receptors to MDMA-induced effects on locomotor behavior patterns in mice.

MDMA or 'ecstasy' (3,4-methylenedioxymethamphetamine) is a commonly used psychoactive drug that has unusual and distinctive behavioral effects in both humans and animals. In rodents, MDMA administration produces a unique locomotor activity pattern, with high activity characterized by smooth locomotor paths and perseverative thigmotaxis. Although considerable evidence supports a major role for serotonin release in MDMA-induced locomotor activity, dopamine (DA) receptor antagonists have recently been shown to attenuate these effects. Here, we tested the hypothesis that DA D1, D2, and D3 receptors contribute to MDMA-induced alterations in locomotor activity and motor patterns. DA D1, D2, or D3 receptor knockout (KO) and wild-type (WT) mice received vehicle or (+/-)-MDMA and were tested for 60 min in the behavioral pattern monitor (BPM). D1 KO mice exhibited significant increases in MDMA-induced hyperactivity in the late testing phase as well as an overall increase in straight path movements. In contrast, D2 KO mice exhibited reductions in MDMA-induced hyperactivity in the late testing phase, and exhibited significantly less sensitivity to MDMA-induced perseverative thigmotaxis. At baseline, D2 KO mice also exhibited reduced activity and more circumscribed movements compared to WT mice. Female D3 KO mice showed a slight reduction in MDMA-induced hyperactivity. These results confirm differential modulatory roles for D1 and D2 and perhaps D3 receptors in MDMA-induced hyperactivity. More specifically, D1 receptor activation appears to modify the type of activity (linear vs circumscribed), whereas D2 receptor activation appears to contribute to the repetitive circling behavior produced by MDMA.

Analysis of Variance↗

PubMed2006

Deficit in schizophrenia to recruit the striatum in implicit learning: a functional magnetic resonance imaging investigation.

In schizophrenia, explicit learning deficits have been well established although it is less clear whether these patients have deficits in implicit learning (IL). IL is thought to depend on intact striatal functioning. This study examined the hypothesis that schizophrenia patients show deficient recruitment of striatal activation during an IL paradigm, relative to performance-matched healthy comparison subjects. Ten subjects with schizophrenia on atypical antipsychotic medication and 10 age, gender, education, and performance matched healthy comparison subjects underwent fMRI while performing an IL task. On the basis of whole-brain and striatal region-of-interest analyses, we found a relative lack of striatal activation in schizophrenia patients. This result is consistent with convergent evidence of striatal dysfunction in schizophrenia.

Adult↗

PubMed2006

An insular view of anxiety.

We propose a general hypothesis that integrates affective and cognitive processing with neuroanatomy to explain anxiety pronenes. The premise is that individuals who are prone to anxiety show an altered interoceptive prediction signal, i.e., manifest augmented detection of the difference between the observed and expected body state. As a consequence, the increased prediction signal of a prospective aversive body state triggers an increase in anxious affect, worrisome thoughts and other avoidance behaviors. The anterior insula is proposed to play a key role in this process. Further testing of this model--which should include investigation of genetic and environmental influences--may lead to the development of novel treatments that attenuate this altered interoceptive prediction signal in patients with anxiety disorders.

Anxiety↗

PubMed2006

Illicit drug use and anxiety disorders: findings from two community surveys.

The focus of this investigation was the relationship between anxiety disorders and lifetime use of amphetamines, cocaine, hallucinogens and heroin in two contemporaneous samples. Data from two independent community surveys conducted in the US (N=5877) and Ontario (N=8116) were used to assess whether a lifetime anxiety disorder diagnosis (social phobia, panic disorder, agoraphobia, specific phobia, and generalized anxiety disorder) was significantly associated with lifetime use of amphetamines, hallucinogens, cocaine, and heroin. Posttraumatic stress disorder was assessed only in the US survey. After controlling for sociodemographics, a significant association between any anxiety disorder diagnosis and lifetime stimulant use, cocaine use, and hallucinogen use was found in both surveys (OR approximately 1.5-3.0). Any anxiety disorder diagnosis was significantly associated with lifetime heroin use in the US survey (OR approximately 3.0). Clinicians and researchers need to be aware of the relationship between anxiety disorders and illicit drug use.

Adolescent↗

PubMed2006

Anterior cingulate activity modulates nonlinear decision weight function of uncertain prospects.

Prospect theory developed by Kahneman and Tversky has been among the most influential psychological models and explains many nonnormative decision-making phenomena, e.g. why people play the lottery or bet on long-shots. A Certainty Equivalent procedure was used during functional magnetic resonance imaging to identify the neural substrates that are important for nonlinear transformation of probabilities to decision weights. Differential activation in the anterior cingulate cortex during high versus low probability prospects correlated (r = 0.84, P < 0.01) with the degree of the nonlinearity of the transformation of probabilities to decision weights, which indicates that risk-seeking behavior for low probability prospects and risk-averse decision-making for mid to high probability prospects may be due to a lack of controlled processing by the anterior cingulate cortex.

Adult↗

PubMed2006

Effects of two nights sleep deprivation and two nights recovery sleep on response inhibition.

This study examined the effects of two nights of total sleep deprivation (TSD) and two nights of recovery sleep on response inhibition. Thirty-eight young, healthy adults performed a Go-NoGo task at 14 : 00 after: (1) a normal night of sleep; (2) each of two consecutive nights of TSD; and (3) each of two consecutive nights of recovery sleep; they also performed the task at 05 : 00 during the first night of sleep deprivation. We hypothesized that TSD would lead to an impaired ability to withhold a response that would be reversed with recovery sleep. Subjects did experience a significant increase in false positive responses throughout all of TSD, errors of omission (i.e. missed 'go' targets) were not significant until after the second night of TSD. Both components (withholding a response and automatic responding) of the task returned to baseline levels after one night of recovery sleep. These data suggest that individuals experience difficulty in withholding an inappropriate response during TSD, even when they are able to attend to the incoming stimuli and respond accurately to appropriate stimuli.

Adult↗

PubMed2006

Alcohol attenuates load-related activation during a working memory task: relation to level of response to alcohol.

BACKGROUND: A low level of response to alcohol is a major risk factor for the development of alcohol dependence, but neural correlates of this marker are unclear. METHOD: Ten healthy volunteers were classified by median split on level of response to alcohol and underwent 2 sessions of functional magnetic resonance imaging following ingestion of a moderate dose of alcohol and a placebo. The blood oxygen level-dependent activation to an event-related visual working memory test was examined. RESULTS: The subjects exhibited longer response latencies and more errors as a function of increasing working memory load and showed a load-dependent increase in activation in dorsolateral prefrontal cortex, posterior parietal cortex, and visual cortex. Alcohol did not affect performance (errors or response latency), but attenuated the working memory load-dependent activation in the dorsolateral prefrontal cortex. During the placebo condition, individuals with a low level of response to alcohol showed greater activation in dorsolateral prefrontal cortex and posterior parietal cortex than those with a high level of response to alcohol. During the alcohol condition, groups showed similar attenuation of load-dependent brain activation in these regions. CONCLUSION: Low-level responders relative to high-level responders exhibited an increased working memory load-dependent activation in dorsolateral prefrontal cortex and posterior parietal cortex when not exposed to alcohol. This increase in brain response was attenuated in low-level responders after ingesting a moderate dose of alcohol.

Adult↗

PubMed2005

Affective ambiguity for a group recruits ventromedial prefrontal cortex.

Affective appraisal often involves processing complex and ambiguous stimuli, such as the mood of a group people. However, affective neuroimaging research often uses individual faces as stimuli when exploring the neural circuitry involved in social appraisal. Results from studies using single face paradigms may not generalize to settings where multiple faces are simultaneously processed. The goal of the current study was to use a novel task that presents groups of affective faces to probe the medial prefrontal cortex (PFC), a region that is critically involved in appraisal of ambiguous affective stimuli, in healthy volunteers. In the current study, 27 subjects performed the Wall of Faces (WOF) task in which multiple matrices of faces were briefly presented during functional MRI. Subjects were asked to decide whether there were more angry or happy faces (emotional decision) or whether there were more male or female faces (gender decision). In each condition, the array contained either an equal (ambiguous trials) or an unequal (unambiguous trials) distribution of one affect or gender. Ambiguous trials relative to unambiguous trials activated regions implicated in conflict monitoring and cognitive control, including the dorsal anterior cingulate cortex (ACC), dorsolateral PFC, and posterior parietal cortex. When comparing ambiguous affective decisions with ambiguous gender decisions, the ventromedial PFC (including the ventral ACC) was significantly more active. This supports the dissociation of the ACC into dorsal cognitive and ventral affective divisions, and suggests that the ventromedial PFC may play a critical role in appraising affective tone in a complex display of multiple human faces.

Adolescent↗

PubMed2005

The role of the striatum in implicit learning: a functional magnetic resonance imaging study.

Previous research has posited striatal involvement in implicit learning. However, imaging studies have not directly compared learners with non-learners. Using functional magnetic resonance imaging with 15 study participants, we used an implicit learning task previously associated with striatal recruitment. Dorsal and ventral striatum activation was observed in the eight participants who demonstrated implicit learning. Ventral striatum activations occurred to a greater extent in implicit learning versus non-implicit learning participants, and were correlated with the degree of reaction time advantage in implicit learning participants, even after controlling for general decreases in reaction time over time. These findings strengthen the specificity of the striatum in implicit learning and are suggestive of a dissociation of striatal regions relative to elements of implicit learning performance.

Adolescent↗

PubMed2005

Neurobiology of decision making: a selective review from a neurocognitive and clinical perspective.

We present a temporal map of key processes that occur during decision making, which consists of three stages: 1) formation of preferences among options, 2) selection and execution of an action, and 3) experience or evaluation of an outcome. This framework can be used to integrate findings of traditional choice psychology, neuropsychology, brain lesion studies, and functional neuroimaging. Decision making is distributed across various brain centers, which are differentially active across these stages of decision making. This approach can be used to follow developmental trajectories of the different stages of decision making and to identify unique deficits associated with distinct psychiatric disorders.

Animals↗