Jeffrey N. Valdez

Images of desire: Food-craving activation during fMRI

Food craving (defined as an intense desire to eat a specific food) is of interest because it is extremely common and because it influences obesity or nutritional status. It has also been suggested that food craving may be the evolutionary source for cravings of all kinds including cravings for drugs and alcohol. Yet, little is known about the functional neuroanatomy of food craving. We report here the first functional magnetic resonance imaging (fMRI) study to explicitly examine food craving. A two-part technique was used to produce the food cravings. Threshold was reduced through a diet manipulation (monotonous diet) and cravings were triggered during blood oxygenation level-dependent (BOLD) fMRI sessions by having subjects imagine the sensory properties of favorite foods (a cue-induction technique). Subjects were also asked to imagine the monotonous diet (which they did not crave). Diet condition had an activating effect on both behavioral (reports of craving) and fMRI measures. Craving-related changes in fMRI signal were identified in the hippocampus, insula, and caudate, three areas reported to be involved in drug craving. Thus, this work supports the common substrate hypothesis for food and drug cravings.

Baby schema modulates the brain reward system in nulliparous women

Ethologist Konrad Lorenz defined the baby schema (“Kindchenschema”) as a set of infantile physical features, such as round face and big eyes, that is perceived as cute and motivates caretaking behavior in the human, with the evolutionary function of enhancing offspring survival. The neural basis of this fundamental altruistic instinct is not well understood. Prior studies reported a pattern of brain response to pictures of children, but did not dissociate the brain response to baby schema from the response to children. Using functional magnetic resonance imaging and controlled manipulation of the baby schema in infant faces, we found that baby schema activates the nucleus accumbens, a key structure of the mesocorticolimbic system mediating reward processing and appetitive motivation, in nulliparous women. Our findings suggest that engagement of the mesocorticolimbic system is the neurophysiologic mechanism by which baby schema promotes human caregiving, regardless of kinship.

Alterations of fronto-temporal connectivity during word encoding in schizophrenia

Cognitive deficits, including impaired verbal memory, are prominent in schizophrenia and lead to increased disability. Functional neuroimaging of patients with schizophrenia performing memory tasks has revealed abnormal activation patterns in prefrontal cortex and temporo-limbic regions. Aberrant fronto-temporal interactions thus represent a potential pathophysiological mechanism underlying verbal memory deficits, yet this hypothesis of disturbed connectivity is not tested directly with standard activation studies. We performed within-subject correlations of frontal and temporal timeseries to measure functional connectivity during verbal encoding. Our results confirm earlier findings of aberrant fronto-temporal connectivity in schizophrenia, and extend them by identifying distinct alterations within dorsal and ventral prefrontal cortex. Relative to healthy controls, patients with schizophrenia had reduced connectivity between the dorsolateral prefrontal cortex (DLPFC) and temporal lobe areas including parahippocampus and superior temporal gyrus. In contrast, patients showed increased connectivity between a region of ventrolateral prefrontal cortex (VLPFC) and these same temporal lobe regions. Higher temporal-DLPFC connectivity during encoding was associated with better subsequent recognition accuracy in controls, but not patients. Temporal-VLPFC connectivity was uncorrelated with recognition accuracy in either group. The results suggest that reduced temporal-DLPFC connectivity in schizophrenia could underlie encoding deficits, and increased temporal-VLPFC connectivity may represent an ineffective compensatory effort.

“It’s not what you say, but how you say it” : A reciprocal temporo-frontal network for affective prosody

Humans communicate emotion vocally by modulating acoustic cues such as pitch, intensity and voice quality. Research has documented how the relative presence or absence of such cues alters the likelihood of perceiving an emotion, but the neural underpinnings of acoustic cue-dependent emotion perception remain obscure. Using functional magnetic resonance imaging in 20 subjects we examined a reciprocal circuit consisting of superior temporal cortex, amygdala and inferior frontal gyrus that may underlie affective prosodic comprehension. Results showed that increased saliency of emotion-specific acoustic cues was associated with increased activation in superior temporal cortex [planum temporale (PT), posterior superior temporal gyrus (pSTG), and posterior superior middle gyrus (pMTG)] and amygdala, whereas decreased saliency of acoustic cues was associated with increased inferior frontal activity and temporo-frontal connectivity. These results suggest that sensory-integrative processing is facilitated when the acoustic signal is rich in affective information, yielding increased activation in temporal cortex and amygdala. Conversely, when the acoustic signal is ambiguous, greater evaluative processes are recruited, increasing activation in inferior frontal gyrus (IFG) and IFG STG connectivity. Auditory regions may thus integrate acoustic information with amygdala input to form emotion-specific representations, which are evaluated within inferior frontal regions.

Effect of abstinence challenge on brain function and cognition in smokers differs by COMT genotype

The val allele of the catechol-O-methyltransferase (COMT) val158met polymorphism has been linked with nicotine dependence and with cognitive performance in healthy volunteers. We tested the hypothesis that the val allele is a risk factor for altered brain function and cognition during nicotine abstinence as compared with the normal smoking state. Chronic smokers (n=33) were genotyped prospectively for the COMT polymorphism for balanced selection of met/met, val/met and val/val groups. A visual N-back working memory task was performed during two separate blood oxygen level-dependent (BOLD) functional magnetic resonance imaging sessions in counterbalanced order: (1) smoking as usual, and (2)⩾14 h confirmed abstinence. Significant genotype by session interactions were observed for BOLD signal in right dorsolateral prefrontal cortex (DLPFC; (P=0.0005), left DLPFC (P=0.02) and dorsal cingulate/medial prefrontal cortex (P=0.01) as well as for task reaction time (P=0.03). Smokers with val/val genotypes were more sensitive to the abstinence challenge than carriers of the met allele, with the greatest effects on BOLD signal and performance speed at the highest working memory load. These data suggest a novel brain–behavior mechanism that may underlie the increased susceptibility to nicotine dependence and smoking relapse associated with the COMT val allele. Exploration of the effects of COMT inhibitors as a possible smoking cessation aid in this group may be warranted.

Association of Enhanced Limbic Response to Threat With Decreased Cortical Facial Recognition Memory Response in Schizophrenia

OBJECTIVE Recognition memory of faces is impaired in patients with schizophrenia, as is the neural processing of threat-related signals, but how these deficits interact to produce symptoms is unclear. The authors used an affective face recognition paradigm to examine possible interactions between cognitive and affective neural systems in schizophrenia. METHOD Blood-oxygen-level-dependent response was examined by means of functional magnetic resonance imaging (3 Tesla) in healthy comparison subjects (N=21) and in patients with schizophrenia (N=12) or schizoaffective disorder, depressed type (N=4), during a two-choice recognition task that used images of human faces. Each target face, previously displayed with a threatening or nonthreatening affect, was displayed with neutral affect. Responses to successful recognition and responses to the effect of previously threatening versus nonthreatening affect were evaluated, and correlations with symptom severity (total Brief Psychiatric Rating Scale score) were examined. Functional connectivity analyses examined the relationship between activation in the amygdala and cortical regions involved in recognition memory. RESULTS Patients performed the task more slowly than healthy comparison subjects. Comparison subjects recruited the expected cortical regions to a greater degree than patients, and patients with more severe symptoms demonstrated proportionally less recruitment. Increased symptoms were also correlated with augmented amygdala and orbitofrontal cortex response to threatening faces. Comparison subjects exhibited a negative correlation between activity in the amygdala and cortical regions involved in cognition, while patients showed weakening of this relationship. CONCLUSION Increased symptoms were related to an enhanced threat response in limbic regions and a diminished recognition memory response in cortical regions, supporting a link between these two brain systems that are often examined in isolation. This finding suggests that abnormal processing of threat-related signals in the environment may exacerbate cognitive impairment in schizophrenia.

Effect of Retrieval Effort and Switching Demand on fMRI Activation During Semantic Word Generation in Schizophrenia

Verbal fluency deficits in schizophrenia are difficult to interpret because the tasks are multi-factorial and groups differ in total words generated. We manipulated retrieval and switching demands by requiring alternation between over-learned sequences in which retrieval is relatively automatic (OS) and semantic categories requiring increased retrieval effort (SC). Controlled processing was also manipulated by including switching and non-switching conditions, and formal thought disorder (FTD) was assessed with the communication disorders index (CDI). The OS/SC semantic fluency paradigm was administered during fMRI to 13 patients with schizophrenia and 14 matched controls. Images were acquired on a 3 Tesla Siemens scanner using compressed image acquisition to allow for cued overt word production. Subjects alternated between OS, SC, OS-switch, SC-switch, and baseline blocks. Images were pre-processed in SPM-2, and a two-stage random effects analysis tested within and between group contrasts. There were no group performance differences. fMRI analysis did not reveal any group differences during the OS non-switching condition. Both groups produced expected activation in bilateral prefrontal and inferior parietal regions. However, during the SC condition patients had greater activation than controls in left prefrontal, right anterior cingulate, right superior temporal, bilateral thalamus, and left parietal regions. There was also evidence of patient over-activation in prefrontal, superior temporal, superior parietal, and visual association areas when a switching component was added. FTD was negatively correlated with BOLD response in the right anterior cingulate, cuneus and superior frontal gyrus during increased retrieval demand, and positively correlated with fMRI activation in the left lingual gyrus, right fusiform gyrus and left superior parietal lobule during increased switching demand. These results indicate that patients are able to successfully perform effortful semantic fluency tasks during non-speeded conditions. When retrieval is relatively automatic there does not appear to be an effect of schizophrenia on fMRI response. However, when retrieval and controlled processing demands increase, patients have greater activation than controls despite unimpaired task performance. This inefficient BOLD response may explain why patients are slower and less accurate on standard self-paced fluency tasks.

Functional magnetic resonance imaging of internal source monitoring in schizophrenia: recognition with and without recollection.

Patients with schizophrenia tend to have impaired source monitoring and intact item recognition, suggesting an over-reliance of familiarity effects. We previously demonstrated that providing patients with a levels-of-processing (LOP) semantic encoding strategy normalized source monitoring. The current blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) study tests the hypothesis that patients will have abnormally increased fronto-temporal activation despite intact performance. fMRI was measured in 13 patients and 13 demographically matched healthy controls during a LOP source monitoring paradigm. SPM2 was used for standard pre-processing and statistical analyses, with a corrected significance threshold of p<.05. Examination of accuracy and speed measures did not reveal any group differences in task performance. Regardless of source retrieval success both groups activated expected prefrontal and parietal regions, with no areas of relatively greater control versus patient activation. In support of the hypothesis, patients showed abnormally increased activation in temporolimbic areas including middle and superior temporal gyrus, thalamus, and parahippocampal gyrus. Activation in these areas was associated with worse positive and negative symptoms, but did not correlate with performance, suggesting inefficient rather than compensatory activation.

Not Pitch Perfect: Sensory Contributions to Affective Communication Impairment in Schizophrenia

BACKGROUND Schizophrenia patients have vocal affect (prosody) deficits that are treatment resistant and associated with negative symptoms and poor outcome. The neural correlates of this dysfunction are unclear. Prior study has suggested that schizophrenia vocal affect perception deficits stem from an inability to use acoustic cues, notably pitch, in decoding emotion. METHODS Functional magnetic resonance imaging was performed in 24 schizophrenia patients and 28 healthy control subjects, during the performance of a four-choice (happiness, fear, anger, neutral) vocal affect identification task in which items for each emotion varied parametrically in affective salient acoustic cue levels. RESULTS We observed that parametric increases in cue levels in schizophrenia failed to produce the same identification rate increases as in control subjects. These deficits correlated with diminished reciprocal activation changes in superior temporal and inferior frontal gyri and reduced temporo-frontal connectivity. Task activation also correlated with independent measures of pitch perception and negative symptom severity. CONCLUSIONS These findings illustrate the interplay between sensory and higher-order cognitive dysfunction in schizophrenia. Sensory contributions to vocal affect deficits also suggest that this neurobehavioral marker could be targeted by pharmacological or behavioral remediation of acoustic feature discrimination.

Ventrolateral prefrontal cortex and the effects of task demand context on facial affect appraisal in schizophrenia

Schizophrenia patients display impaired performance and brain activity during facial affect recognition. These impairments may reflect stimulus-driven perceptual decrements and evaluative processing abnormalities. We differentiated these two processes by contrasting responses to identical stimuli presented under different contexts. Seventeen healthy controls and 16 schizophrenia patients performed an fMRI facial affect detection task. Subjects identified an affective target presented amongst foils of differing emotions. We hypothesized that targeting affiliative emotions (happiness, sadness) would create a task demand context distinct from that generated when targeting threat emotions (anger, fear). We compared affiliative foil stimuli within a congruent affiliative context with identical stimuli presented in an incongruent threat context. Threat foils were analysed in the same manner. Controls activated right orbitofrontal cortex (OFC)/ventrolateral prefrontal cortex (VLPFC) more to affiliative foils in threat contexts than to identical stimuli within affiliative contexts. Patients displayed reduced OFC/VLPFC activation to all foils, and no activation modulation by context. This lack of context modulation coincided with a 2-fold decrement in foil detection efficiency. Task demands produce contextual effects during facial affective processing in regions activated during affect evaluation. In schizophrenia, reduced modulation of OFC/VLPFC by context coupled with reduced behavioural efficiency suggests impaired ventral prefrontal control mechanisms that optimize affective appraisal.