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Biomedical subjects

J E Desmond

Publications and source records attributed to J E Desmond.

At least 19 recordsLinked to original sources

Contribution of alcohol abuse to cerebellar volume deficits in men with schizophrenia.

BACKGROUND: It is controversial whether cerebellar tissue volume deficits occur in schizophrenia and, if so, what regions and tissue types are affected. Complicating such investigations is the high incidence of alcoholism comorbidity in patients with schizophrenia that itself can contribute to cerebellar abnormalities. METHOD: We studied 61 healthy men (control subjects), 25 men with alcoholism, 27 men with schizophrenia, and 19 men comorbid for schizophrenia and alcoholism with the use of magnetic resonance imaging. Cerebellar structures were outlined manually, tissue classification was determined statistically, and regional volumes were corrected for normal variation in head size and age. RESULTS: Patients with schizophrenia alone had enlarged fourth ventricles (1.5 SD relative to controls) but showed no cerebellar tissue volume deficits. The alcoholic group had gray and white matter vermian deficits (-0.5 SD), most prominent in anterior superior lobules, and gray matter hemisphere deficits (-0.8 SD), but not fourth ventricle enlargement. The comorbid group had cerebellar hemisphere (-1.3 SD) and vermian gray matter volume deficits (-0.7 SD) and fourth ventricular enlargement (1.6 SD); these abnormalities were greater than in either single-diagnosis group, despite significantly lower levels of alcohol consumption compared with the alcoholic group. Gray matter volume in the anterior superior vermis correlated with lifetime alcohol consumption in the schizophrenic and comorbid groups when combined. CONCLUSIONS: Cerebellar tissue volume deficits were detected in schizophrenia only when accompanied by alcoholism. By contrast, fourth ventricular enlargement occurred in schizophrenia even without alcoholism, although it was exacerbated by alcoholism. These findings support a model of cerebellar supersensitivity to alcohol-related tissue volume deficits in schizophrenia.

Adult↗

Cerebellar volume decline in normal aging, alcoholism, and Korsakoff's syndrome: relation to ataxia.

The authors used magnetic resonance imaging to measure gray and white matter volumes in cerebellar hemispheres and 4 vermian regions in 61 normal control (NC) men aged 23-72 years, 25 men with uncomplicated alcoholism (ALC), and 8 men and 1 woman with alcoholic Korsakoff s syndrome (KS). NC and ALC took quantitative gait and balance tests. Gray but not white matter volume declined with normal age in both hemispheres and anterior-superior vermis. ALC had gray but not white matter cerebellar hemisphere volume deficits, whereas KS had deficits in both tissue types. ALC and KS had gray and white matter volume deficits in anterior superior but not posterior inferior vermis. ALC had a 1 SD ataxia deficit, significantly and selectively correlated with white matter volume in anterior superior vermis. Regional distribution but not severity of cerebellar volume deficits is similar in alcoholic individuals whether or not complicated by KS and relates to ataxia.

Adult↗

Functional magnetic resonance imaging evidence for right-hemisphere involvement in processing unusual semantic relationships.

Brain areas active in generating usual (typical) or unusual (atypical) noun-verb relations were examined using functional magnetic resonance imaging. Seven adults generated the 1st verb to come to mind (usual verb) in response to novel and repeated nouns (priming test) and then generated either an unusual verb or the 1st verb to come to mind in response to novel nouns (unusual test). The left inferior prefrontal cortex (LIPC) and right cerebellum were more active when generating usual verbs to novel nouns than to repeated nouns. When participants generated unusual verbs, there was no increased activation in LIPC, but there was increased activity in the right middle and superior frontal gyri, left middle frontal gyrus, and bilateral cerebellum. Results support theories that the right hemisphere is involved in the processing of distant associations that may be useful in creative thought and problem solving.

Adult↗

Time course of odorant-induced activation in the human primary olfactory cortex.

Paradoxically, attempts to visualize odorant-induced functional magnetic resonance imaging (fMRI) activation in the human have yielded activations in secondary olfactory regions but not in the primary olfactory cortex-piriform cortex. We show that odorant-induced activation in primary olfactory cortex was not previously made evident with fMRI because of the unique time course of activity in this region: in primary olfactory cortex, odorants induced a strong early transient increase in signal amplitude that then habituated within 30-40 s of odorant presence. This time course of activation seen here in the primary olfactory cortex of the human is almost identical to that recorded electrophysiologically in the piriform cortex of the rat. Mapping activation with analyses that are sensitive to both this transient increase in signal amplitude, and temporal-variance, enabled us to use fMRI to consistently visualize odorant-induced activation in the human primary olfactory cortex. The combination of continued accurate odorant detection at the behavioral level despite primary olfactory cortex habituation at the physiological level suggests that the functional neuroanatomy of the olfactory response may change throughout prolonged olfactory stimulation.

Adult↗

Verb generation priming involves conceptual implicit memory.

Brain activation patterns differ and generation latencies are reduced when generating verbs to repeated nouns (Raichle et al., 1994). Amnesic participants show normal magnitude of priming (Seger et al., 1997). Despite its importance in neuropsychology, verb generation priming is not well characterized psychologically. Six behavioral studies found that verb generation priming was specific to the verb rather than to the noun or the noun-verb pair, was equivalent after overt or covert generation and after reading verbs or generating verbs, was affected by levels of processing, and transferred completely across languages in bilinguals. These results indicate that verb generation priming involves priming of particular responses and happens at a conceptual level. These findings provide new insights about the significance of brain imaging and neuropsychological studies involving verb generation priming.

Analysis of Variance↗

Convergent cortical representation of semantic processing in bilinguals.

This study examined whether semantic processes in two languages (English and Spanish) are mediated by a common neural system in fluent bilinguals who acquired their second language years after acquiring their first language. Functional magnetic resonance imaging was performed while bilingual participants made semantic and nonsemantic decisions about words in Spanish and English. There was greater activation for semantic relative to nonsemantic decisions in left and right frontal regions, with greater left frontal activation. The locations of activations were similar for both languages, and no differences were found when semantic decisions for English and Spanish words were compared directly. These results demonstrate a shared frontal lobe system for semantic analysis of the languages and are consistent with cognitive research on bilingualism indicating that the two languages of a bilingual person access a common semantic system.

Adult↗

Load-dependent roles of frontal brain regions in the maintenance of working memory.

Brain imaging studies have suggested a critical role for prefrontal cortex in working memory (WM) tasks that require both maintainenance and manipulation of information over time in delayed-response WM tasks. In the present study, functional magnetic resonance imaging (fMRI) was used to examine whether prefrontal areas are activated when only maintenance is required in a delayed-response WM task, without the overt requirement to manipulate the stored information. In two scans, six subjects performed WM tasks in which, on each trial, they (1) encoded 1, 3, or 6 to-be-remembered letters, (2) maintained these letters across a 5-second unfilled delay, and (3) determined whether a single probe letter was or was not part of the memory set. Activation of left caudal inferior frontal gyrus was observed, relative to the 1-letter task, when subjects were required to maintain 3 letters in WM. When subjects were required to maintain 6 letters in WM, additional prefrontal areas, most notably middle and superior frontal gyri, were activated bilaterally. Thus, increasing the amount of to-be-maintained information, without any overt manipulation requirement, resulted in the recruitment of wide-spread frontal-lobe regions. Inferior frontal gyrus activation was left-hemisphere dominant in both the 3- and 6-letter conditions, suggesting that such activation reflected material-specific verbal processes. Activation in middle and superior frontal gyri appeared only in the 6-letter condition and was right-hemisphere dominant, suggesting that such activation reflected material-independent executive processes.

Adult↗

Functional specialization for semantic and phonological processing in the left inferior prefrontal cortex.

Neuroimaging and neuropsychological studies have implicated left inferior prefrontal cortex (LIPC) in both semantic and phonological processing. In this study, functional magnetic resonance imaging was used to examine whether separate LIPC regions participate in each of these types of processing. Performance of a semantic decision task resulted in extensive LIPC activation compared to a perceptual control task. Phonological processing of words and pseudowords in a syllable-counting task resulted in activation of the dorsal aspect of the left inferior frontal gyrus near the inferior frontal sulcus (BA 44/45) compared to a perceptual control task, with greater activation for nonwords compared to words. In a direct comparison of semantic and phonological tasks, semantic processing preferentially activated the ventral aspect of the left inferior frontal gyrus (BA 47/45). A review of the literature demonstrated a similar distinction between left prefrontal regions involved in semantic processing and phonological/lexical processing. The results suggest that a distinct region in the left inferior frontal cortex is involved in semantic processing, whereas other regions may subserve phonological processes engaged during both semantic and phonological tasks.

Brain Mapping↗

Blind smell: brain activation induced by an undetected air-borne chemical.

EEG and behavioural evidence suggests that air-borne chemicals can affect the nervous system without being consciously detected. EEG and behaviour, however, do not specify which brain structures are involved in chemical sensing that occurs below a threshold of conscious detection. Here we used functional MRI to localize brain activation induced by high and low concentrations of the air-borne compound oestra-1,3,5(10),16-tetraen-3yl acetate. Following presentations of both concentrations, eight of eight subjects reported verbally that they could not detect any odour (P = 0.004). Forced choice detection performed during the presentations revealed above-chance detection of the high concentration, but no better than chance detection of the low concentration compound. Both concentrations induced significant brain activation, primarily in the anterior medial thalamus and inferior frontal gyrus. Activation in the inferior frontal gyrus during the high concentration condition was significantly greater in the right than in the left hemisphere (P = 0.03). A trend towards greater thalamic activation was observed for the high concentration than the low concentration compound (P = 0.08). These findings localize human brain activation that was induced by an undetectable air-borne chemical (the low concentration compound).

Adult↗

In vivo mammillary body volume deficits in amnesic and nonamnesic alcoholics.

BACKGROUND: Neuropathological studies use the presence of mammillary body (MB) pathology as a cardinal, diagnostic feature of Wernicke's encephalopathy (WE) in neuropsychiatric diseases, most notably alcoholism. Although Korsakoffs Syndrome (KS), which is marked behaviorally by dense global amnesia, is a typical sequela of WE, it remains controversial whether these two conditions necessarily co-occur and whether MB pathology is therefore a diagnostic requisite for KS. METHODS: We investigated these issues by examining, in vivo, 24 nonamnesic alcoholics (ALC), 5 amnesic alcoholics (KS), and 51 normal controls with three-dimensional MRI and memory testing. MB volume was determined from successive, 1 mm thick slices. RESULTS: The ALC group had significantly smaller MB volumes bilaterally (mean = 54.5 +/- 22.0 mm3) than controls (mean = 66.3 +/- 17.1 mm3), and the KS group had even smaller MB volumes than the ALC group (mean = 20.7 +/- 14.8 mm3). Only 2 ALC patients met historical clinical criteria for past WE, and their MB volumes were well within range of the remaining 22 ALC patients. Although all five KS patients met historical clinical criteria for WE, three KS did not have accompanying dementia and had the same degree of MB volume loss as the ALC; the remaining two KS had accompanying dementia and MB volumes half the volume of the ALC group and of KS patients without dementia. CONCLUSIONS: These findings provide volumetric in vivo evidence that: (1) MB volume deficits do occur in alcoholics without amnesia, although these deficits are not present in ail such alcoholics; (2) greater MB volume deficits are present in alcoholics with clinically detectable amnesia or dementia; (3) MB shrinkage is related to severity of cognitive and memory dysfunction, which suggests a continuum of MB pathology in chronic alcoholism to KS; and (4) the presence of WE in all of the KS patients and in the two ALC patients with the greatest long-term declarative memory deficit supports the possibility of an additional and unique pathology distinguishing nonamnesic and amnesic alcoholism.

Adult↗

Selective effects of methylphenidate in attention deficit hyperactivity disorder: a functional magnetic resonance study.

Functional MRI revealed differences between children with Attention Deficit Hyperactivity Disorder (ADHD) and healthy controls in their frontal-striatal function and its modulation by methylphenidate during response inhibition. Children performed two go/no-go tasks with and without drug. ADHD children had impaired inhibitory control on both tasks. Off-drug frontal-striatal activation during response inhibition differed between ADHD and healthy children: ADHD children had greater frontal activation on one task and reduced striatal activation on the other task. Drug effects differed between ADHD and healthy children: The drug improved response inhibition in both groups on one task and only in ADHD children on the other task. The drug modulated brain activation during response inhibition on only one task: It increased frontal activation to an equal extent in both groups. In contrast, it increased striatal activation in ADHD children but reduced it in healthy children. These results suggest that ADHD is characterized by atypical frontal-striatal function and that methylphenidate affects striatal activation differently in ADHD than in healthy children.

Adolescent↗

Material-specific lateralization of prefrontal activation during episodic encoding and retrieval.

Although numerous neuroimaging studies have examined the functional neuroanatomy supporting episodic memory for verbal material, there have been few investigations of non-verbal episodic encoding and retrieval. We used fMRI to directly compare prefrontal activation elicited by verbal and non-verbal material during encoding and during retrieval. Regardless of the mnemonic operation (encoding/retrieval), inferior prefrontal activation lateralized based on material type. Verbal encoding and retrieval resulted in greater left inferior prefrontal activation, whereas non-verbal encoding and retrieval resulted in greater right inferior prefrontal activation. The similarity between inferior prefrontal activity during encoding and during retrieval indicates that these mnemonic operations depend on shared processes mediated by inferior prefrontal regions.

Acoustic Stimulation↗

Odorant-induced and sniff-induced activation in the cerebellum of the human.

Functional magnetic resonance imaging was used to test whether odorants induce activation in the cerebellum of the human. The odorants vanillin and propionic acid both induced significant activation, primarily in the posterior lateral hemispheres. Activation was concentration-dependent, greater after stimulation with higher concentration odorants. By contrast, the action of sniffing nonodorized air induced significant activation in the anterior cerebellum, primarily in the central lobule. These findings demonstrate that the cerebellum plays a role in human olfaction. A hypothesis is proposed whereby the cerebellum maintains a feedback mechanism that regulates sniff volume in relation to odor concentration.

Adult↗

Hemispheric asymmetry for emotional stimuli detected with fMRI.

Current brain models of emotion processing hypothesize that positive (or approach-related) emotions are lateralized towards the left hemisphere, whereas negative (or withdrawal-related) emotions are lateralized towards the right hemisphere. Brain imaging studies, however, have so far failed to document such hemispheric lateralization. In a functional magnetic resonance imaging (fMRI) study, 14 female subjects viewed alternating blocks of emotionally valenced positive and negative pictures. When the experience of valence was equated for arousal, overall brain reactivity was lateralized towards the left hemisphere for positive pictures and towards the right hemisphere for negative pictures. This study provides direct support for the valence hypothesis, under conditions of equivalent arousal, by means of functional brain imaging.

Adult↗

Making memories: brain activity that predicts how well visual experience will be remembered.

Experiences are remembered or forgotten, but the neural determinants for the mnemonic fate of experience are unknown. Event-related functional magnetic resonance imaging was used to identify specific brain activations that differentiated between visual experiences that were later remembered well, remembered less well, or forgotten. During scanning of medial temporal lobe and frontal lobe regions, subjects viewed complex, color photographs. Subjects later received a test of memory for the photographs. The magnitudes of focal activations in right prefrontal cortex and in bilateral parahippocampal cortex predicted which photographs were later remembered well, remembered less well, or forgotten.

Adult↗

Sniffing and smelling: separate subsystems in the human olfactory cortex.

The sensation and perception of smell (olfaction) are largely dependent on sniffing, which is an active stage of stimulus transport and therefore an integral component of mammalian olfaction. Electrophysiological data obtained from study of the hedgehog, rat, rabbit, dog and monkey indicate that sniffing (whether or not an odorant is present) induces an oscillation of activity in the olfactory bulb, driving the piriform cortex in the temporal lobe, in other words, the piriform is driven by the olfactory bulb at the frequency of sniffing. Here we use functional magnetic resonance imaging (fMRI) that is dependent on the level of oxygen in the blood to determine whether sniffing can induce activation in the piriform of humans, and whether this activation can be differentiated from activation induced by an odorant. We find that sniffing, whether odorant is present or absent, induces activation primarily in the piriform cortex of the temporal lobe and in the medial and posterior orbito-frontal gyri of the frontal lobe. The source of the sniff-induced activation is the somatosensory stimulation that is induced by air flow through the nostrils. In contrast, a smell, regardless of sniffing, induces activation mainly in the lateral and anterior orbito-frontal gyri of the frontal lobe. The dissociation between regions activated by olfactory exploration (sniffing) and regions activated by olfactory content (smell) shows a distinction in brain organization in terms of human olfaction.

Adult↗

The role of left prefrontal cortex in language and memory.

This article reviews attempts to characterize the mental operations mediated by left inferior prefrontal cortex, especially the anterior and inferior portion of the gyrus, with the functional neuroimaging techniques of positron emission tomography and functional magnetic resonance imaging. Activations in this region occur during semantic, relative to nonsemantic, tasks for the generation of words to semantic cues or the classification of words or pictures into semantic categories. This activation appears in the right prefrontal cortex of people known to be atypically right-hemisphere dominant for language. In this region, activations are associated with meaningful encoding that leads to superior explicit memory for stimuli and deactivations with implicit semantic memory (repetition priming) for words and pictures. New findings are reported showing that patients with global amnesia show deactivations in the same region associated with repetition priming, that activation in this region reflects selection of a response from among numerous relative to few alternatives, and that activations in a portion of this region are associated specifically with semantic relative to phonological processing. It is hypothesized that activations in left inferior prefrontal cortex reflect a domain-specific semantic working memory capacity that is invoked more for semantic than nonsemantic analyses regardless of stimulus modality, more for initial than for repeated semantic analysis of a word or picture, more when a response must be selected from among many than few legitimate alternatives, and that yields superior later explicit memory for experiences.

Amnesia↗