Brain activation, response inhibition, and increased risk for substance use disorder

Background:  Youth at high risk for developing substance use disorders (SUDs) often exhibit differences which suggest inhibitory impairments when compared to average risk youth.
Methods:  To examine the underlying neural activity related to these impairments, functional MRI (fMRI) was employed in adolescents during an antisaccade task requiring inhibition of an eye movement response. Each subject's level of neurobehavioral disinhibition (ND) was assessed using a multi-informant, multi-method approach, which has been shown to be highly predictive of SUD onset. The fMRI data was categorized into neural regions of interest according to total frontal, parietal, occipital, and temporal lobe activation.
Results:  Results demonstrated that ND score was negatively correlated with total amount of frontal activation, but was not significantly correlated with total activation in any other neural region.
Conclusions:  These results indicate deficits in frontal activation in youth with high amounts of ND, suggesting a possible developmental delay of executive processes in high-risk youth.     

fMRI BOLD response to the eyes task in offspring from multiplex alcohol dependence families

Background:  Increased susceptibility for developing alcohol dependence (AD) may be related to structural and functional differences in brain circuits that influence social cognition and more specifically, theory of mind (ToM). Alcohol dependent individuals have a greater likelihood of having deficits in social skills and greater social alienation. These characteristics may be related to inherited differences in the neuroanatomical network that comprises the social brain.
Methods:  Adolescent/young adult participants from multiplex AD families and controls ( n  = 16) were matched for gender, age, IQ, education, and handedness and administered the Eyes Task of Baron-Cohen during functional magnetic resonance imaging (fMRI).
Results:  High-risk (HR) subjects showed significantly diminished blood oxygen level dependent (BOLD) response in comparison with low-risk control young adults in the right middle temporal gyrus (RMTG) and the left inferior frontal gyrus (LIFG), areas that have previously been implicated in ToM tasks.
Conclusions:  Offspring from multiplex families for AD may manifest one aspect of their genetic susceptibility by having a diminished BOLD response in brain regions associated with performance of ToM tasks. These results suggest that those at risk for developing AD may have reduced ability to empathize with others' state of mind, possibly resulting in diminished social skill.     

Quantitative prediction of perceptual decisions during near-threshold fear detection

A fundamental goal of cognitive neuroscience is to explain how mental decisions originate from basic neural mechanisms. The goal of the present study was to investigate the neural correlates of perceptual decisions in the context of emotional perception. To probe this question, we investigated how fluctuations in functional MRI (fMRI) signals were correlated with behavioral choice during a near-threshold fear detection task. fMRI signals predicted behavioral choice independently of stimulus properties and task accuracy in a network of brain regions linked to emotional processing: posterior cingulate cortex, medial prefrontal cortex, right inferior frontal gyrus, and left insula. We quantified the link between fMRI signals and behavioral choice in a whole-brain analysis by determining choice probabilities by means of signal-detection theory methods. Our results demonstrate that voxel-wise fMRI signals can reliably predict behavioral choice in a quantitative fashion (choice probabilities ranged from 0.63 to 0.78) at levels comparable to neuronal data. We suggest that the conscious decision that a fearful face has been seen is represented across a network of interconnected brain regions that prepare the organism to appropriately handle emotionally challenging stimuli and that regulate the associated emotional response.     

Alterations in Brain Serotonin Synthesis in Male Alcoholics Measured Using Positron Emission Tomography

Background:  A consistent association between low endogenous 5HT function and high alcohol preference has been observed, and a number of serotonergic manipulations (uptake blockers, agonists) alter alcohol consumption in animals and humans. Studies have also shown an inverse relationship between alcohol use and cerebrospinal fluid levels of serotonin metabolites, suggesting that chronic alcohol consumption produces alterations in serotonin synthesis or release.
Methods:  The objective of the study was to characterize regional brain serotonin synthesis in nondepressed chronic alcoholics at treatment entry in comparison to normal nonalcoholic controls using PET and the tracer α-[¹¹C]-methyl- l -tryptophan.
Results:  Comparisons of the alcoholics and controls by SPM found that there were significant differences in the rate of serotonin synthesis between groups. Serotonin synthesis was significantly lower among alcoholics in Brodmann Area (BA) 9, 10, and 32. However, serotonin synthesis among the alcoholics group was significantly higher than controls at BA19 in the occipital lobe and around the transverse temporal convolution in the left superior temporal gyrus (BA41). In addition, there were correlations between regional serotonin synthesis and a quantity-frequency measure of alcohol consumption. Regions showing a significant negative correlation with QF included the bilateral rectus gyri (BA11) in the orbitofrontal area, the bilateral medial frontal area (BA6), and the right amygdala.
Conclusions:  Current alcoholism is associated with serotonergic abnormalities in brain regions that are known to be involved in planning, judgment, self-control, and emotional regulation.     

Neural deficits in children with dyslexia ameliorated by behavioral remediation: evidence from functional MRI

Developmental dyslexia, characterized by unexplained difficulty in reading, is associated with behavioral deficits in phonological processing. Functional neuroimaging studies have shown a deficit in the neural mechanisms underlying phonological processing in children and adults with dyslexia. The present study examined whether behavioral remediation ameliorates these dysfunctional neural mechanisms in children with dyslexia. Functional MRI was performed on 20 children with dyslexia (8-12 years old) during phonological processing before and after a remediation program focused on auditory processing and oral language training. Behaviorally, training improved oral language and reading performance. Physiologically, children with dyslexia showed increased activity in multiple brain areas. Increases occurred in left temporo-parietal cortex and left inferior frontal gyrus, bringing brain activation in these regions closer to that seen in normal-reading children. Increased activity was observed also in right-hemisphere frontal and temporal regions and in the anterior cingulate gyrus. Children with dyslexia showed a correlation between the magnitude of increased activation in left temporo-parietal cortex and improvement in oral language ability. These results suggest that a partial remediation of language-processing deficits, resulting in improved reading, ameliorates disrupted function in brain regions associated with phonological processing and produces additional compensatory activation in other brain regions.     

Blockade of cue-induced brain activation of abstinent alcoholics by a single administration of amisulpride as measured with fMRI

BACKGROUND: Once alcohol dependence is established, alcohol-associated cues may induce dopamine release in the reward system, which is accompanied by alcohol craving and may lead to relapse. In cocaine addicts, dopamine release in the thalamus was positively correlated with cocaine craving. We tested the effects of the atypical dopamine D(2/3) blocker amisulpride on cue-induced brain activation in a functional magnetic resonance imaging (fMRI) paradigm. METHODS: Alcohol-associated and neutral pictures were presented in a block design to 10 male abstinent alcoholics (1-3 weeks after detoxification) and 10 healthy men during fMRI. The fMRI scans were acquired before and 2 hours after the oral application of 400 mg amisulpride. Before and after each scan, alcohol craving was measured with visual analogue scales. RESULTS: Before the application of amisulpride, alcohol versus control cues elicited a higher blood oxygen level-dependent (BOLD) signal in the left frontal and orbitofrontal lobe, left cingulate gyrus, bilateral parietal lobe, and bilateral hippocampus in alcoholics compared with healthy controls. After amisulpride, alcoholics showed a reduced activation in the right thalamus compared with the first scan. Alcoholics no longer showed significant differences in their cue-elicited BOLD response after amisulpride medication compared with medication-free controls. Self-reported craving was not affected by amisulpride medication. CONCLUSIONS: Amisulpride medication was associated with reduced cue-induced activation of the thalamus, a brain region closely connected with frontostriatal circuits that regulate behavior and may influence relapse risk.     

Sex differences in brain activation elicited by humor

With recent investigation beginning to reveal the cortical and subcortical neuroanatomical correlates of humor appreciation, the present event-related functional MRI (fMRI) study was designed to elucidate sex-specific recruitment of these humor related networks. Twenty healthy subjects (10 females) underwent fMRI scanning while subjectively rating 70 verbal and nonverbal achromatic cartoons as funny or unfunny. Data were analyzed by comparing blood oxygenation-level-dependent signal activation during funny and unfunny stimuli. Males and females share an extensive humor-response strategy as indicated by recruitment of similar brain regions: both activate the temporal-occipital junction and temporal pole, structures implicated in semantic knowledge and juxtaposition, and the inferior frontal gyrus, likely to be involved in language processing. Females, however, activate the left prefrontal cortex more than males, suggesting a greater degree of executive processing and language-based decoding. Females also exhibit greater activation of mesolimbic regions, including the nucleus accumbens, implying greater reward network response and possibly less reward expectation. These results indicate sex-specific differences in neural response to humor with implications for sex-based disparities in the integration of cognition and emotion.     

Greater Activation in Left Hemisphere Language‐Related Regions During Simple Judgment Tasks Among Substance‐Dependent Patients in Treatment for Alcoholism

Background: Alcoholism is often associated with impaired emotional control. Alcoholics have also been found to have deficits in frontal lobe executive functions. Recent functional imaging studies have suggested that alcoholics show greater activation than nonalcoholics in circuits involving frontal lobes, as well as more posterior brain regions, when engaged in executive‐type tasks. In this study, we compared brain activations of alcohol‐dependent patients and healthy nonalcoholics while they performed 2 simple judgment tasks designed to activate frontal circuits involved in a basic form of decision making. Participants completed 1 judgment task that required an emotional judgment and 1 task that did not, which enabled us to study whether alcoholics had greater brain activation while performing executive tasks, and to determine if emotional tasks elicited even greater activation than nonemotional tasks. Methods: We performed functional magnetic resonance imaging scans while alcoholic patients and nonalcoholic controls viewed pictures from the International Affective Picture System. In 3 separate runs, participants viewed the images without making a judgment, determined whether the images were indoor or outdoor scenes, or decided if they liked or disliked the images. Results: There was little difference in brain activation between alcoholics and controls when no judgment was required. When participants made judgments about either the location or whether they liked or disliked an image, however, we observed significantly increased activation in frontal, limbic, and temporal regions in the patients relative to the controls. Increases were particularly robust in the frontal lobe and in areas of the brain associated with language. When we compared the emotional to the nonemotional judgment, the alcoholics, but not the controls, showed greater activation in the ventral mesial frontal cortex. Conclusions: Alcoholic patients appear to use brain language areas more than nonalcoholics while making judgments about the setting or liking of emotionally arousing visual images. This increased activation may reflect a compensatory recruitment of brain regions to perform simple decision‐making tasks.     

Verb generation in patients with focal frontal lesions: A neuropsychological test of neuroimaging findings

What are the neural bases of semantic memory? Traditional beliefs that the temporal lobes subserve the retrieval of semantic knowledge, arising from lesion studies, have been recently called into question by functional neuroimaging studies finding correlations between semantic retrieval and activity in left prefrontal cortex. Has neuroimaging taught us something new about the neural bases of cognition that older methods could not reveal or has it merely identified brain activity that is correlated with but not causally related to the process of semantic retrieval? We examined the ability of patients with focal frontal lesions to perform a task commonly used in neuroimaging experiments, the generation of semantically appropriate action words for concrete nouns, and found evidence of the necessity of the left inferior frontal gyrus for certain components of the verb generation task. Notably, these components did not include semantic retrieval per se.     

Increased distractibility by task-irrelevant sound changes in abstinent alcoholics

Background: Chronic alcoholism is accompanied by "frontal" neuropsychological deficits that include an inability to maintain focus of attention. This might be associated with pronounced involuntary attention shifting to task-irrelevant stimulus changes and, thereafter, an impaired reorienting to the relevant task. The neural abnormalities that underlie such deficits in alcoholics were explored with event-related potential (ERP) components that disclosed different phases of detection and orienting to stimulus changes.
Methods: Twenty consecutive abstinent male alcoholics (DSM-IV) and 20 age-matched male controls (healthy social drinkers) were instructed to discriminate equiprobable 100 and 200 msec tones in a reaction-time task (RT) and to ignore occasional, either slight (7%) or wide (70%), frequency changes (hypothesized to increase RT) during an ERP measurement.
Results: In the alcoholics, we found pronounced distractibility, evidenced by a RT lag ( p < 0.01) caused by deviants, that correlated (Spearman ρ= 0.5) with a significantly enhanced ( p < 0.01) amplitude of mismatch negativity (MMN) to deviants. Significantly increased RT lag for trials subsequent to deviants (slight p < 0.001, wide p < 0.05) in the alcoholics suggested impaired reorienting to the relevant task. The MMN enhancement also predicted poorer hit rates in the alcoholics (Spearman ρ= 0.6–0.7). Both the MMN enhancement and pronounced distractibility correlated (Spearman ρ= 0.4) with an early onset of alcoholism.
Conclusions: Attentional deficits in the abstinent alcoholics were indicated by the increased distractibility by irrelevant sound changes. The MMN enhancement suggested that this reflects impaired neural inhibition of involuntary attention shifting, being most pronounced in early-onset alcoholics.     

Cross-language differences in the brain network subserving intelligible speech

How is language processed in the brain by native speakers of different languages? Is there one brain system for all languages or are different languages subserved by different brain systems? The first view emphasizes commonality, whereas the second emphasizes specificity. We investigated the cortical dynamics involved in processing two very diverse languages: a tonal language (Chinese) and a nontonal language (English). We used functional MRI and dynamic causal modeling analysis to compute and compare brain network models exhaustively with all possible connections among nodes of language regions in temporal and frontal cortex and found that the information flow from the posterior to anterior portions of the temporal cortex was commonly shared by Chinese and English speakers during speech comprehension, whereas the inferior frontal gyrus received neural signals from the left posterior portion of the temporal cortex in English speakers and from the bilateral anterior portion of the temporal cortex in Chinese speakers. Our results revealed that, although speech processing is largely carried out in the common left hemisphere classical language areas (Broca’s and Wernicke’s areas) and anterior temporal cortex, speech comprehension across different language groups depends on how these brain regions interact with each other. Moreover, the right anterior temporal cortex, which is crucial for tone processing, is equally important as its left homolog, the left anterior temporal cortex, in modulating the cortical dynamics in tone language comprehension. The current study pinpoints the importance of the bilateral anterior temporal cortex in language comprehension that is downplayed or even ignored by popular contemporary models of speech comprehension.The brain of a newborn discriminates the various phonemic contrasts used in different languages (1) by recruiting distributed cortical regions (2); by 6–10 mo, it is preferentially tuned to the phonemes in native speech that they have been exposed to (3, 4). In adult humans, the key neural nodes that subserve speech comprehension are located in the superior temporal cortex (5, 6) and the inferior frontal cortex (7). Do these regions interact in different ways depending on the type of language that is being processed? Little is known about how information flows among these critical language nodes in native speakers of different languages.As one of the unique capacities of the human brain (8), the nature of compositional languages and their neural mechanisms have been the interests of scientific research for decades. There are more than 7,000 different spoken languages in the world today used for communication. By exploring the brain networks subserving universal properties across languages and specific differences within different languages, such research helps address the essential questions in neurolinguistics such as the constitution of knowledge of language, as well as how it is acquired (9). Although traditional universal grammar theory argues that functional components of linguistic ability are manifest without being taught (10), recent connectionist theory within a neural network approach emphasizes interactions among primary systems of neuronal processing units that support language acquisition and use, where the weights of connections among these units are gradually changed during learning and thus highly constrained by the unique feature of a given language (9, 11, 12). Related with connectionist views, the dual pathway model of language based on evidence from neuroimaging and anatomical studies was also framed to interpret the neural basis of language comprehension and production (13, 14), especially in speech comprehension.Intelligible speech is processed hierarchically in human neocortex, with the anterior temporal (13, 15, 16) and frontal cortices (Broca’s area) operating at a higher hierarchical level than the posterior region centered on superior temporal sulcus/gyrus (pSTS/pSTG, core of Wernicke’s area), which itself receives inputs from primary and secondary auditory cortices (17). In the dual ventral-dorsal pathway model, the dorsal-stream pathway of speech processing assumes primary processing begins in the posterior region of the temporal cortex and is then sent through the dorsal part to the temporal-parietal cortex before finally reaching the frontal cortex for a sound-motor projection. The ventral-stream pathway assumes processing starts on the ventral side of the temporal lobe and then proceeds to the anterior regions, before reaching the frontal cortex for a sound-meaning mapping (7, 18).The cortical regions that process speech are likely to be common across languages, but how these regions interact with each other in the cortical pathway may depend on the distinctive phonetic-linguistic characteristics in different languages. Based on the connectionist approach, previous cross-language studies investigated the behavioral consequence of processing different languages with a distinction such as pitch accent processing (19). The current study aims to explore the dynamic neural networks of processing intelligible speech in two different languages with a featured phonological-semantic variant: Mandarin Chinese and English. These two languages are the most widely spoken languages in the world, but differ in several aspects such as the use of lexical tones. In tonal languages like Mandarin Chinese, suprasegmental features, i.e., different pitch patterns, serve to distinguish lexical meaning, whereas in nontonal languages, pitch changes are less complex and do not convey lexical information. Except the lexical tone, Mandarin Chinese includes more homophones than English, which also makes the sound-meaning mapping in Mandarin dependent more on tone and context information during speech and thus may place higher demands on the ventral pathway of the related neural network. To test this hypothesis, we examined the cortical dynamics underlying speech comprehension for two groups of native speakers of English and Mandarin languages.We used functional MRI (fMRI) and dynamic causal modeling (DCM) (20) to first investigate the cortical dynamics among the left posterior region of superior temporal gyrus (pSTG), anterior region of superior temporal gyrus (aSTG), and inferior frontal gyrus (IFG) of native speakers in Chinese (a tonal language) compared with English (a nontonal language) with an identical experimental design. Thirty native Chinese speakers and 26 native English speakers with matched age, sex, and handedness (all right-handed) were scanned while presented with intelligible and unintelligible speech of their native languages (either Mandarin Chinese or English) in blocks, spoken by a male and a female. Subjects were instructed only to judge the gender of the speakers. The data of native English speakers were reanalyzed from a previous study (21). The brain activation of the intelligibility effect and the effective connectivity among the three left hemisphere brain regions were analyzed for both language groups under identical procedures and then put together for comparison.     

Reduced fronto-cerebellar functional connectivity in chronic alcoholic patients

Background: Alcohol dependence is associated with neurocognitive deficits related to neuropathological changes in structure, metabolism, and function of the brain. Impairments of motor functioning in alcoholics have been attributed to well‐characterized neuropathological brain abnormalities in cerebellum. Methods: Using functional magnetic resonance imaging (fMRI), we studied in vivo the functional connectivity between cerebellar and cortical brain regions. Participants were 10 uncomplicated chronic alcoholic patients studied after 5 to 7 days of abstinence when signs of withdrawal had abated and 10 matched healthy controls. We focused on regions of prefrontal, frontal, temporal, and parietal cortex that exhibited an fMRI response associated with nondominant hand finger tapping in the patients but not in the controls. We predicted that fronto‐cerebellar functional connectivity would be diminished in alcoholics compared with controls. Results: Functional connectivity in a circuit involving premotor areas (Brodmann Area 6) and Lobule VI of the superior cerebellum was reduced in the patients compared with the controls. Functional connectivity was also reduced in a circuit involving prefrontal cortex (Brodmann Area 9) and Lobule VIII of the inferior cerebellum. Reductions in connectivity were specific to fronto‐cerebellar circuits and were not found in other regions examined. Conclusions: Our findings show a pattern in recently abstinent alcoholic patients of specific deficits in functional connectivity and recruitment of additional brain regions for the performance of a simple finger‐tapping task. A small sample, differences in smoking, and a brief abstinence period preclude definitive conclusions, but this pattern of diminished fronto‐cerebellar functional connectivity is highly compatible with the characteristic neuropathological lesions documented in alcoholics and may reflect brain dysfunction associated with alcoholism.     

Brain activation in response to visual sexual stimuli in male patients with right middle cerebral artery infarction: The first case-control functional magnetic resonance imaging study

Sexual dysfunction is a common problem after cerebral infarction; however, little is known about sexual arousal in poststroke patients. Thus, this study aimed to investigate brain activation in response to visual sexual stimuli in patients with right middle cerebral artery (MCA) territory infarction using functional magnetic resonance imaging (fMRI). Using fMRI in 20 participants (11 right MCA infarction patients and 9 age-matched healthy controls), we assessed brain activation elicited by visual sexual stimuli (erotic images) and visual nonsexual stimuli (landscape images). In right MCA infarction patients, the left dorsolateral prefrontal cortex and the left frontal subgyral area were more strongly activated by visual sexual stimuli than by nonvisual sexual stimuli. Brain areas that were more activated by visual sexual stimuli in right MCA infarction patients than in controls included the right parahippocampal gyrus and the bilateral frontal subgyral area. These fMRI results suggest that brain activation patterns in response to visual sexual stimuli might be influenced by right MCA infarction. Further research is needed to explore the association between sexual dysfunction and brain activation in poststroke patients.     

Cerebral processing of auditory stimuli in patients with irritable bowel syndrome

AIM: To determine by brain functional magnetic resonance imaging (fMRI) whether cerebral processing of non-visceral stimuli is altered in irritable bowel syndrome (IBS) patients compared with healthy subjects. To circumvent spinal viscerosomatic convergence mechanisms, we used auditory stimulation, and to identify a possible influence of psychological factors the stimuli differed in their emotional quality. METHODS: In 8 IBS patients and 8 controls, fMRI measurements were performed using a block design of 4 auditory stimuli of different emotional quality (pleasant sounds of chimes, unpleasant peep (2000 Hz), neutral words, and emotional words). A gradient echo T2*-weighted sequence was used for the functional scans. Statistical maps were constructed using the general linear model. RESULTS: To emotional auditory stimuli, IBS patients relative to controls responded with stronger deactiva-tions in a greater variety of emotional processing regions, while the response patterns, unlike in controls, did not differentiate between distressing or pleasant sounds. To neutral auditory stimuli, by contrast, only IBS patients responded with large significant activations. CONCLUSION: Altered cerebral response patterns to auditory stimuli in emotional stimulus-processing regions suggest that altered sensory processing in IBS may not be specific for visceral sensation, but might reflect generalized changes in emotional sensitivity and affective reactivity, possibly associated with the psychological comorbidity often found in IBS patients.     

Effects of family history of alcohol use disorders on spatial working memory BOLD response in adolescents

Background:  A positive family history (FH) of alcohol use disorders (AUD) has been linked to increased risk for the development of AUD, and neurocognitive factors have been postulated as important underlying mechanisms of familial alcoholism transmission.
Methods:  We used functional magnetic resonance imaging (fMRI) during a spatial working memory (SWM) and vigilance paradigm to investigate potential neurodevelopmental differences linked to familial density of AUD in 72 adolescents aged 12 to 14 years.
Results:  Youth with denser family histories of AUD showed less activation during a simple vigilance condition relative to SWM in cingulate and medial frontal gyri (β = 0.28, p  = 0.03), and a trend for more relative activity during rest (β = −0.25, p  = 0.07) in this cluster.
Conclusions:  Youth with greater familial densities of AUD may be less successful at modulating activity of the default network, potentially indicating a greater propensity for task-independent thought or reduced inhibition of task-irrelevant processing. Failure to moderate activation of the default network may have implications for cognitive efficiency and goal directed behavior in youth with dense FH. Further, aberrant activation in cingulate regions may be linked to genetic variation in GABA receptor units, suggesting a useful endophenotype for risk associated with alcohol dependence.     

缺血性卒中后非流利型失语患者局部一致性变化：静息态功能性磁共振成像研究

目的 探讨缺血性卒中后非流利性失语患者静息态功能磁共振成像（functionalmagnetic resonance imaging fMRI）的脑功能特点.方法 对17例缺血性卒中后非流利性失语患者以及19名年龄、性别和受教育程度均匹配的健康对照者进行静息态fMRI检查,采用局部区域一致性（regional homogeneity,ReHo）分析方法计算静息态下脑区的ReHo情况.结果 与对照组比较,患者组左侧额上回、右侧额下回、右侧脑岛以及右侧缘上回ReHo值增高,右侧小脑半球、左侧颞上回、颞中回以及右侧颞下回脑区ReHo值降低.结论 在静息状态下,缺血性卒中后非流利性失语患者存在多个脑区ReHo异常,这种异常改变可能与其功能损伤后修复的代偿作用有关.     

Alcohol-related ERP changes recorded from different modalities: a topographic analysis

BACKGROUND: There is controversy in the literature regarding the relationship between event-related-potential (ERP) abnormalities in abstinent alcoholics and stimulus-processing modality (i.e., visual versus auditory). The first purpose of this study was to address questions about whether ERP abnormalities observed in alcoholics are modality specific. The second purpose was to employ current source density (CSD) analyses to investigate topographic differences between alcoholics and controls within each modality. METHODS: Data were collected from 30 sober male alcoholics and 39 normal males in a typical auditory oddball task and in a visual oddball paradigm with novel stimuli, with an extensive set of 61 scalp electrodes. Visual and quantitative assessment of CSD maps as well as analyses of variances on both raw and normalized ERP data were performed. RESULTS: Positive findings were limited to the N1 and P3 components. The visual N1 amplitude was significantly smaller in alcoholics than in controls at the parietal region; no significant group differences in N1 were found in the auditory modality. Alcoholics had widespread reductions in P3 amplitudes in both modalities compared with controls, although in the frontal region this effect was partially due to the influence of age. These P3 reductions in alcoholics were statistically more pronounced in the posterior compared with the anterior regions regardless of modality. Topographically, sources in CSD maps were weaker in alcoholics than in controls; in the frontal and central regions, the weakness was more pronounced in the auditory modality but, in parietal and occipital regions, it was more pronounced in the visual modality. CONCLUSIONS: The results suggest that, in abstinent alcoholics, abnormalities in auditory ERPs may be localized to more anterior sources, while abnormalities in visual ERPs may be localized to more posterior sources. ERP topographic features are more sensitive than amplitude measurements in assessing alcoholic-related modality effects.     

Neural mechanisms of planning: a computational analysis using event-related fMRI

To investigate the neural mechanisms of planning, we used a novel adaptation of the Tower of Hanoi (TOH) task and event-related functional MRI. Participants were trained in applying a specific strategy to an isomorph of the five-disk TOH task. After training, participants solved novel problems during event-related functional MRI. A computational cognitive model of the task was used to generate a reference time series representing the expected blood oxygen level-dependent response in brain areas involved in the manipulation and planning of goals. This time series was used as one term within a general linear modeling framework to identify brain areas in which the time course of activity varied as a function of goal-processing events. Two distinct time courses of activation were identified, one in which activation varied parametrically with goal-processing operations, and the other in which activation became pronounced only during goal-processing intensive trials. Regions showing the parametric relationship comprised a frontoparietal system and include right dorsolateral prefrontal cortex [Brodmann's area (BA 9)], bilateral parietal (BA 40/7), and bilateral premotor (BA 6) areas. Regions preferentially engaged only during goal-intensive processing include left inferior frontal gyrus (BA 44). The implications of these results for the current model, as well as for our understanding of the neural mechanisms of planning and functional specialization of the prefrontal cortex, are discussed.     

Effects of Prenatal Alcohol Exposure on Brain Activation During an Arithmetic Task: An fMRI Study

Background: While behavioral studies have established that prenatal alcohol exposure (PAE) can result in diminished arithmetic processing capability, the underlying neural correlates of this deficit are still unclear. The aim of the present study was to use functional magnetic resonance imaging to determine the effect of PAE on neuronal activation during a subtraction task. Methods: Participants were young adults from a low socio‐economic status population who were identified prenatally; the sample consisted of healthy unexposed controls (n = 17) and PAE who were subdivided based on the presence (n = 19) or absence of physical dysmorphic signs (n = 18). Multiple regression analysis was used to determine extent of activation and percent signal change during arithmetic processing, using a letter‐matching task as the baseline. Region of interest analysis of activation was performed in the native space and normalized for each individual to compensate for the considerable variability in head size observed in the alcohol‐exposed population. Results: An exposure‐dependent response was observed in task performance and neuronal activation. Dysmorphic PAE individuals showed significantly lower task‐related performance and activation in regions known to be associated with arithmetic processing, including left superior and right inferior parietal regions and medial frontal gyrus, while the nondysmorphic PAE group was generally intermediate but not significantly different from the control group in task performance and activation. Conclusions: Results indicate that there is a range of effects of PAE on arithmetic processing and that the severity of this deficit may be dependent on degree of impairment demonstrated by the exposed individual. Evidence of physical dysmorphia may be indicative of functional damage to regions associated with arithmetic calculation, resulting in markedly impaired neuronal recruitment.     

Differential neural response to alcohol priming and alcohol taste cues is associated with DRD4 VNTR and OPRM1 genotypes

Background:  Studies suggest that polymorphisms in the D4 dopamine receptor (DRD4) and opioid receptor, μ1 (OPRM1) genes are involved in differential response to the effects of alcohol and to alcohol cues. However, to date, the mechanisms that underlie these differences remain largely unknown.
Methods:  Using functional magnetic resonance imaging, hemodynamic response in mesocorticolimbic structures after exposure to alcohol tastes was contrasted with a control taste and compared between DRD4 variable number of tandem repeats (VNTR) genotypes and OPRM1 A118G genotypes. Additionally, the effects of a priming dose of alcohol on this response were examined.
Results:  The results indicated that DRD4 VNTR >7 repeat individuals (DRD4.L) had significantly greater response to alcohol cues in the orbitofrontal cortex, anterior cingulate gyrus, and striatum compared with individuals with <7 repeats (DRD4.S) prior to a priming dose of alcohol ( p  < 0.05), but not after a priming dose. In the OPRM1 comparisons, results showed that individuals with at least 1 copy of the OPRM1 + 118 G allele had greater hemodynamic response in mesocorticolimbic areas both before and after priming compared with those who were homozygous for the OPRM1 + 118 A allele. For the DRD4.L and OPRM1 + 118 G groups, brain response in the striatum was highly correlated with measures of alcohol use and behavior such that greater activity corresponded with greater frequency and quantity of alcohol use.
Conclusions:  The DRD4 VNTR and OPRM1 A118G polymorphisms are associated with functional neural changes in mesocorticolimbic structures after exposure to alcohol cues. This provides evidence for the contributions of the DRD4 and OPRM1 genes in modulating neural activity in structures that are involved in the motivation to drink.