Focus on the brain: HIV infection and alcoholism: comorbidity effects on brain structure and function.
Article Type: Clinical report
Subject: HIV patients (Care and treatment)
HIV infection (Development and progression)
HIV infection (Risk factors)
HIV infection (Research)
HIV infection (Care and treatment)
HIV infection (Complications and side effects)
Alcoholism (Health aspects)
Alcoholism (Research)
Alcoholism (Psychological aspects)
Brain diseases (Risk factors)
Brain diseases (Research)
Authors: Rosenbloom, Margaret J.
Sullivan, Edith V.
Pfefferbaum, Adolf
Pub Date: 09/22/2010
Publication: Name: Alcohol Research & Health Publisher: U.S. Government Printing Office Audience: Academic; Professional Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2010 U.S. Government Printing Office ISSN: 1535-7414
Issue: Date: Fall, 2010 Source Volume: 33 Source Issue: 3
Topic: Event Code: 310 Science & research
Accession Number: 243042496
Full Text: The incidence of alcohol abuse and dependence among individuals infected with human immunodeficiency virus (HIV) is high. Those with concurrent HIV infection and alcohol abuse are at risk of poorer clinical outcome for a variety of reasons that are described in detail elsewhere in this issue of Alcohol Research & Health. HIV infection and excessive alcohol use each have specific negative effects on central nervous system (CNS) structure, chemistry, and function, some of which are unique to each disease and some of which are shared. Thus, the brains of people with a history of excessive alcohol consumption are particularly vulnerable to further insult when newly exposed to the HIV virus. Continued excessive drinking can exacerbate the new liability from HIV infection, especially in those who develop an AIDS-defining event, such as severely low numbers of immune cells (i.e., [CD4.sup.+] T-cell count under 200/[mm.sup.3]) targeted by HIV infection. The many factors affecting this dynamic interaction of effects of alcohol abuse and HIV infection on the brain are challenging to identify and disentangle but are likely to include the following: general health; cognitive status; age at HIV infection; length and severity of alcohol history before HIV infection; quantity, frequency and pattern of alcohol use after HIV infection; the lag between the HIV diagnosis and start of antiretroviral treatment; diligence in medication compliance; and whether other drugs of abuse are used.

One method for identifying how the effects of excessive alcohol use and HIV infection interact in the brain is to follow people with both active alcoholism and HIV infection and to compare changes in their cognition and brain status over time with changes in individuals with only one condition and control subjects with neither condition; this is known as a four-group comparison. Given the human condition, such studies (especially longitudinal ones entailing repeated examination of the same individuals over an extended time) are necessarily naturalistic and not ethically or practically amenable to formal experimental control over relevant variables, such as alcohol or illicit drug use, nutrition, medication, or risky behavior. Nonetheless, cross-sectional comparisons (i.e., examination at a single time of many different individuals) between the four groups can provide provisional answers to the question of how and in what way HIV infection exacerbates the damage caused by pre-existing alcoholism or, conversely, how excessive alcohol use exacerbates the damage caused by pre-existing HIV infection. This analysis is best performed with a study sample in which the comorbid group is comparable in severity of their HIV disease to HIV-only participants and in severity of alcohol disease to alcohol-only participants (see Rosenbloom et al. 2007b). If alcohol exacerbates the effects of HIV infection, the comorbid group would be predicted to demonstrate greater deficits than either single-diagnosis group, especially for those measures that are affected by both diseases. Such compounded effects could be additive in some cases and synergistic in others.

This brief review summarizes evidence of regional CNS damage from neuroimaging studies using noninvasive magnetic resonance (MR) technologies for in vivo examination of brain structure (conventional magnetic resonance imaging [MRI]), white matter fiber integrity (MR diffusion tensor imaging [DTI]), and brain chemistry (MR spectroscopy [MRS]) in people comorbid for alcoholism and HIV infection compared with single-diagnosis groups and unaffected control subjects. (For more information on these technologies, see the textbox.) Overviews of these methods also are detailed elsewhere (Adalsteinsson et al. 2002; Meyerhoff 2001). Also summarized is evidence from neuropsychological studies examining cognitive and motor functions in the four study groups.


Conventional structural MRI studies collect high-resolution images of the whole brain and permit measurement of the size and shape of brain structures and some aspects of brain tissue integrity.

Findings From Subjects With Alcoholism

Structural MRI studies of uncomplicated alcoholism typically report increased size of the cerebrospinal fluid-filled spaces in the brain (e.g., ventricular enlargement) as well as gray matter and white matter volume shrinkage (Fein et al. 2002; Gazdzinski et al. 2005; Pfefferbaum et al. 1992, 2001), most prominent in frontal cortical regions (Cardenas et al. 2007; Pfefferbaum et al. 1997) and subcortical and cerebellar structures (Makris et al. 2008; Sullivan and Pfefferbaum 2009). These volume abnormalities may be dose related (Cardenas et al. 2005; Pfefferbaum et al. 1998), at least partially reversed with extended sobriety (Carlen et al. 1978; O'Neill et al. 2001; Pfefferbaum et al. 1995; Rosenbloom et al. 2007a), and return with relapse to drinking (O'Neill et al. 2001; Pfefferbaum et al. 1995). Damage to the frontal cortex may contribute to impairment in problem solving and inhibiting undesirable and risky behaviors, whereas damage to the cerebellum likely contributes to the difficulties in balance and gait that frequently are observed in alcoholics.

Findings From Subjects With HIV Infection

Structural MRI studies of HIV infection report little to no brain volume abnormalities in asymptomatic HIV-infected individuals, but there is substantial neuropathology in symptomatic cases (i.e., those with clinically detectable' motor, cognitive, or behavioral symptoms) (Aylward et al. 1995; Jernigan et al. 1993). Brain abnormalities include ventricular enlargement, widespread tissue shrinkage, frontal white matter and caudate volume loss (Aylward et al. 1995; Di Sclafani et al. 1997; Stout et al. 1998), and thinning of the cortex (Thompson et al. 2005) and corpus callosum (Pfefferbaum et al. 2006c). The extent of tissue volume shrinkage or ventricular expansion increases with advancing clinical stage, as determined using Centers for Disease Control and Prevention criteria (Di Sclafani et al. 1997; Thompson et al. 2006), and is related to presence or worsening of cognitive deficits (Heaton et al. 1995; Heindel et al. 1994; Stout et al. 1998).

Findings From Subjects With HIV Infection Plus Alcoholism

In a structural MRI study using the four-group method, there was a graded pattern of ventricular enlargement. The total ventricular system of the uncomplicated HIV group was larger than that of controls, the HIV group comorbid with alcoholism was yet larger, and the alcoholism group was the largest of the three patient groups. The pattern of callosal thinning showed a similar graded effect. In the HIV group comorbid for alcoholism, larger volumes of the third ventricle correlated with lower [CD4.sup.+] cell counts. When the HIV group was divided according to whether participants had ever met criteria for AIDS (i.e., an AIDS-defining event or low [CD4.sup.+] T-cell counts [less than or equal to]200/[mm.sup.3]), alcohol abuse was shown to have a dramatically compounding effect in those with HIV+AIDS but not in those with HIV infection who had not suffered an AIDS-defining event (figures 1 and 2). The effect was especially notable in the genu of the corpus callosum and the frontal and body regions of the lateral ventricles (Pfefferbaum et al. 2006c).


DTI yields measures of the microstructural integrity of white matter (Le Bihan 2003) and provides a method to ascertain how various pathologies affect the microstructure of the brain. Studies typically examine DTI metrics in a defined region of white matter, such as the corpus callosum or centrum semiovale, or can examine tissue integrity along a statistically extracted fiber bundle, a procedure known as quantitative fiber tracking (Gerig et al. 2005). Although fiber tracking does not actually identify anatomically specific fibers or fiber bundles, tractography can provide a statistical and graphical representation along the length of fiber bundles (Mori and van Zijl 2002; Rosenbloom and Pfefferbaum 2008). DTI's sensitivity to detection of disruption of microstructural integrity of white matter may provide an early indication of the potential for HIV-associated dementia (Berger and Avison 2001) and signs of insult from co-existing alcoholism (Pfefferbaum et al. 2007a).

Findings From Subjects With Alcoholism

Among alcoholics, DTI has revealed evidence for disruption of microstructural constituents of white matter even in regions appearing normal on conventional structural imaging (Pfefferbaum et al. 2006a; Pfefferbaum and Sullivan 2002). Chronic alcohol abuse also disrupts microstructure in localized regions of white matter, such as the corpus callosum, and widely distributed regions throughout the centrum semiovale (Pfefferbaum et al. 2006a, b) or in right hemisphere white matter tracts linking prefrontal and limbic systems (Harris et al. 2008). A fiber tracking study examining the integrity of a broad range of white matter tracts across the brain found that frontal and superior sites (frontal forceps, internal and external capsules, fornix, and superior cingulate bundle and longitudinal fasciculi) showed greatest abnormalities in alcoholics relative to controls, while more posterior and inferior bundles were relatively spared (Pfefferbaum et al. 2009b). Poor performance on tests of working memory, visuospatial ability, and gait and balance have been linked to compromised white matter microstructure and amount of alcohol drunk in a lifetime in alcoholics (Pfefferbaum et al. 2006a). Disruption of the myelin sheaths may contribute to slowed motor performance by alcoholics (Pfefferbaum et al. 2009b).

Findings From Subjects With HIV-Infection

Examination of HIV-infected individuals with DTI has revealed microstructural abnormalities of the genu and splenium of the corpus callosum and frontal and parietal subcortical white matter related to disease severity (Filippi et al. 2001). Signs of compromised integrity also can be found in regions of white matter appearing normal on conventional MRI (Stebbins et al. 2007). DTI studies have found signs of compromised white matter integrity in normal-appearing periventricular white matter and the corpus callosum that correlated with low [CD4.sup.+] counts and high viral loads in HIV-infected subjects (Filippi et al. 2001).



Fiber tracking analysis revealed that posterior but not anterior corpus callosum fibers are affected in nondemented HIV-infected patients (Pfefferbaum et al. 2009a). Altered DTI metrics, primarily reflecting axonal compromise, have been found in the following fibers bundles:

* The internal and external capsules, which are fiber bundles that course through the striatum and connect corticospinal regions and the cerebral cortex;

* The superior and inferior cingulate bundles that link frontal and subcortical structures; and

* The posterior sectors of the corpus callosum, which links posterior parietal and temporal regions of the left and right hemispheres.

By contrast, pontocerebellar projection fibers were particularly resistant to HIV effects, as were commissural fibers coursing through premotor and sensorimotor callosal sectors (Pfefferbaum et al. 2009a). Cognitive impairment has been related to white matter degradation and is more severe in patients whose HIV infection has progressed to AIDS (Gongvatana et al. 2009). Similarly, slower speed on tests of finger movement and eye-hand coordination is related to degradation of posterior callosal fibers (Pfefferbaum et al. 2007b).

Findings From Subjects With HIV-Infection Plus Alcoholism

A DTI fiber tracking study examined the effects of HIV-alcoholism comorbidity in the four-group model (Pfefferbaum et al. 2007a). The microstructural integrity of fiber bundles coursing through the genu and splenium of the corpus callosum showed evidence of severe compromise in those with alcoholism whose HIV infection history included an AIDS-defining event (figure 3). Measures of DTI provided indirect support for greater disruption of the myelin sheath covering the axon (i.e., fatty cell body that insulates the axon and promotes speed of communication between cells) in alcoholism (Pfefferbaum et al. 2009 b) than of the axon itself as observed in HIV infection (Pfefferbaum et al. 2009^). The functional significance of these callosal fiber tracking measures in the AIDS+alcoholism group was demonstrated by analyses showing that greater degradation of fiber integrity was associated with slower and less dexterous manual motor performance and greater postural instability while standing (Pfefferbaum et al. 2009b).


MRI and DTI are imaging modalities based primarily on the detection of water protons, their immediate environment, and their mobility. Other constituents, including selective metabolites and neurotransmitters, also are present on the proton spectrum but in smaller quantities than water, yet visible using other MR technologies, such as MR spectroscopy (MRS) and MR spectroscopic imaging (MRSI) (Adalsteinsson et al. 2002; Meyerhoff 2001). A substantial body of research using proton MRS and MRSI (also known as chemical shift imaging [CSI]) has revealed declines in N-acetyl aspartate (NAA), a marker of living neurons, in short-term abstinent alcoholics, with change toward normalization of NAA in longer-term abstinent alcoholics (Durazzo et al. 2006). Use of proton MRS in HIV infection has provided evidence for metabolite abnormalities notable in the basal ganglia, even early in the course of HIV infection (Chang et al. 2008). A proton MRSI study of combined disease effects on the parietal-occipital cortex indicated that only the comorbid (HIV+alcoholism) group was affected, exhibiting a significant deficit in NAA (figure 4). Although neither HIV infection nor alcoholism alone resulted in such a deficit, each disease carried a liability that put dually affected individuals at a heightened risk of neuronal compromise (Pfefferbaum et al. 2005).

In addition to proton ([sup.1]H) spectroscopy, other resonances (e.g., carbon [[sup.13]C] and phosphorous [[sup.31]P]) that provide unique brain metabolic information can be studied, albeit with difficulty because of their low spectral signal (i.e., low signal-to-noise ratio). A [sup.31]P MRS study (see Meyerhoff 2001) noted a cumulative but not interactive or synergistic effect of HIV infection and alcoholism. The symptomatic HIV group and the alcoholic group both had low concentrations of the brain energy metabolites associated with cell membrane breakdown (phosphodiester) and building (phosphocreatine) in superior white matter, and individuals with both conditions had augmented metabolite deficits (Meyerhoff et al. 1995).


An extensive literature is available that describes patterns of neuropsychological impairment associated with alcoholism (for reviews, see Oscar-Berman and Marinkovic 2007; Sullivan 2000) and HIV infection (see Special Section, "HIV/NeuroAIDS" in Neuropsychology Review, June 2009). Significantly fewer studies have considered the effects of HIV+alcoholism comorbidity on cognitive and motor functioning, but an emerging literature indicates that such comorbidity exerts selective rather than simply global adverse effects on component processes of functions. To date, functions examined and found to be disproportionately affected by the combined diseases include speeded performance involving finger movements and eye-hand coordination (i.e., visuomotor speed) (Fama et al. 2007; Rothlind et al. 2005), sustained attention (Sassoon et al. 2007), conflict resolution and attentional allocation (Schulte et al. 2008), associative learning (Sassoon et al. 2007), immediate episodic memory (Fama et al. 2009), and speeded finger movements (Fama et al. 2007).


Brain regions likely contributing to performance on these tasks and known to be disrupted by alcoholism or HIV infection independently or by their combination include the following:

* The frontostriatal system, which is required for working memory, psychomotor speeded activities, and conflict resolution;

* The frontoparietal system, which is the basis of selective attentional and visuospatial networks; and

* The frontocerebellar system, which contributes to verbal and spatial working memory, smooth and speeded motor function, and postural stability.


A useful neuropsychological model to explain some of the results is based on the observation that alcoholism has a frontocerebellar substrate of dysfunction, whereas HIV infection has a frontostriatal substrate of dysfunction. Tasks invoking both of these circuits and the tracts linking these regions (figure 5) may be at particular at risk of disruption from both conditions (Pfefferbaum et al. 2002).


The combined effects of alcoholism and HIV infection on brain structure, chemistry, and function are most devastating in individuals who have experienced an AIDS-defining event. This negative synergism suggests that alcohol is particularly toxic to the HIV-infected brain after a certain stage of the disease; similarly, the alcoholic brain is particularly susceptible to the effects of AIDS. These effects place dually affected individuals at compounded risk for brain functional and structural insult even prior to developing clinically defined dementia, thereby highlighting the relevance of examining groups affected by both conditions (see Fein et al. 1995; Meyerhoff 2001; Pfefferbaum et al. 2007a; Pfefferbaum et al. 2002; Rothlind et al. 2005). The substantial effect of the alcoholism-AIDS interaction on ventricular volumes and callosal size and microstructure, in the context of the modest changes observed in non AIDS, non-alcohol-abusing HIV-infected individuals, highlights the need to consider alcohol use disorders as a major risk factor for developing neuropathology among HIV-infected persons (Pfefferbaum et al. 2007^). Further, the high prevalence of alcoholism in HIV-infected individuals and the interfering effect of alcohol abuse on HIV pharmacological response and therapy compliance underscore the need to recognize the independent and synergistic contributions of each condition to brain structure and function (Pfefferbaum et al. 2006c). The extent to which the deficits in patients with comorbid HIV infection and alcoholism are reversible with abstinence from alcohol and careful adherence to antiretroviral treatments requires investigation using longitudinal study.



This work was support by National Institute on Alcohol Abuse and Alcoholism grants AA-012999, AA-017347, AA-005965, AA-012388, and AA-017168.


The authors declare that they have no competing financial interests.


ADALSTEINSSON, E.; SULLIVAN, E.V.; AND PFEFFERBAUM, A. Biochemical, functional and microstructural magnetic resonance imaging (MRI). In: Liu, Y., and Lovinger, D.M., Eds. Methods in Alcohol-Related Neuroscience Research. Boca Raton, FL: CRC Press, 2002, pp. 345-372.

AYLWARD, E.H.; BRETTSCHNEIDER, P.D.; MCARTHUR, J.C.; ET AL. Magnetic resonance imaging measurement of gray matter volume reductions in HIV dementia. American Journal of Psychiatry 152:987-994, 1995. PMID: 7793469

CARDENAS, VA.; STUDHOLME, C.; GAZDZINSKI, S.; ET AL. Deformation-based morphometry of brain changes in alcohol dependence and abstinence. NeuroImage 34:879-887, 2007. PMID: 17127079

CARDENAS, VA.; STUDHOLME, C.; MEYERHOFF, D.J.; ET AL. Chronic active heavy drinking and family history of problem drinking modulate regional brain tissue volumes. Psychiatry Research 138:115-130, 2005. PMID: 15766635

CARLEN, P.L.; WORTZMAN, G.; HOLGATE, R.C.; ET AL. Reversible cerebral atrophy in recently abstinent chronic alcoholics measured by computed tomography scans. Science 200:1076-1078, 1978. PMID: 653357

CHANG, L.; WONG, V.; NAKAMA, H.; ET AL. Greater than age-related changes in brain diffusion of HIV patients after 1 year. Journal of Neuroimmune Pharmacology 3(4):265-274, 2008. PMID: 18709469

DI SCLAFANI, V.; MACKAY, R.D.; MEYERHOFF, D.J.; ET AL. Brain atrophy in HIV infection is more strongly associated with CDC clinical stage than with cognitive impairment. Journal of the International Neuropsychological Society 3:276-287, 1997. PMID: 9161107

DURAZZO, T.C.; GAZDZINSKI, S.; ROTHLIND, J.C.; ET AL. Brain metabolite concentrations and neurocognition during short-term recovery from alcohol dependence: Preliminary evidence of the effects of concurrent chronic cigarette smoking. Alcoholism: Clinical and Experimental Research 30:539-551, 2006. PMID: 16499496

FAMA, R.; EISEN, J.C.; ROSENBLOOM, M.J.; ET AL. Upper and lower limb motor impairments in alcoholism, HIV-infection, and their comorbidity. Alcoholism: Clinical and Experimental Research 31:1038-1044, 2007. PMID: 17403062

FAMA, R.; ROSENBLOOM, M.J.; NICHOLS, B.N.; ET AL. Working and episodic memory in HIV infection, alcoholism, and their comorbidity: Baseline and 1year follow-up examinations. Alcoholism: Clinical and Experimental Research 33:1815-1824, 2009. PMID: 19656122

FEIN, G.; BIGGINS, C.A.; AND MACKAY, S. Alcohol abuse and HIV infection have additive effects on frontal cortex function as measured by auditory evoked potential P3A latency. Biological Psychiatry 37:183-195, 1995. PMID: 7727627

FEIN, G.; Dl SCLAFANI, V.; CAREDENAS, V.A.; ET AL. Cortical gray matter loss in treatment-naive alcohol dependent individuals. Alcoholism: Clinical and Experimental Research 26:558-564, 2002. PMID: 11981133

FILIPPI, C.G.; ULUG, A.M.; RYAN, E.; ET AL. Diffusion tensor imaging of patients with HIV and normal-appearing white matter on MR images of the brain. American Journal of Neuroradiology 22:277-283, 2001. PMID: 11156769

GAZDZINSKI, S.; DURAZZO, T.C.; AND MEYERHOFF, D.J. Temporal dynamics and determinants of whole brain tissue volume changes during recovery from alcohol dependence. Drug and Alcohol Dependence 78:263-273, 2005. PMID: 15893157

GERIG, G.; COROUGE, I.; VACHET, C.; ET AL. Quantitative analysis of diffusion properties of white matter fiber tracts: A validation study. In: 13th Proceedings of the International Society for Magnetic Resonance in Medicine. Miami, FL. p Abstract no. 1337, 2005

GONGVATANA, A.; SCHWEINSBURG, B.C.; TAYLOR, M.J.; ET AL. White matter tract injury and cognitive impairment in human immunodeficiency virus infected individuals. Journal of Neurovirology 15:187-195, 2009. PMID: 19306228

HARRIS, G.J.; JAFFIN, S.K.; HODGE, S.M.; ET AL. Frontal white matter and cingulum diffusion tensor imaging deficits in alcoholism. Alcoholism: Clinical and Experimental Research 32:1001-1013 2008. PMID: 18422840

HEATON, R.K.; GRANT, I.; BUTTERS, N.; ET AL. The HNRC 500: Neuropsychology of HIV infection at different disease stages. HIV Neurobehavioral Research Center. Journal of the International Neuropsychological Society 1:231-251, 1995. PMID: 9375218

HEINDEL, W.C.; JERNIGAN, T.L.; ARCHIBALD, S.L.; ET AL. The relationship of quantitative brain magnetic resonance imaging measures to neuropathologic indexes of human immunodeficiency virus infection. Archives of Neurology 51:1129-1135, 1994. PMID: 7980109

JERNIGAN, T.L.; ARCHIBALD, S.; HESSELINK, J.R.; ET AL. Magnetic resonance imaging morphometric analysis of cerebral volume loss in human immunodeficiency virus infection. The HNRC Group. Archives of Neurology 50:250-255, 1993. PMID: 8442702

LE BIHAN, D. Looking into the functional architecture of the brain with diffusion MRI. Nature Reviews. Neuroscience 4:469-480, 2003. PMID: 12778119

MAKRIS, N.; OSCAR-BERMAN, M.; JAFFIN, S.K.; ET AL. Decreased volume of the brain reward system in alcoholism. Biological Psychiatry 64(3):192-202, 2008. PMID: 18374900

MEYERHOFF, D.J. Effects of alcohol and HIV infection on the central nervous system. Alcohol Research & Health 25:288-298, 2001. PMID: 11910707

MEYERHOFF, D.J.; MACKAY, S.; SAPPEY-MARINIER, D.; ET AL. Effects of chronic alcohol abuse and HIV infection on brain phosphorus metabolites. Alcoholism: Clinical and Experimental Research 19:685-692, 1995. PMID: 7573794

MORI, S., AND VAN ZIJL, P.C. Fiber tracking: Principles and strategies: A technical review. NMR in Biomedicine 15:468-480, 2002. PMID: 12489096

O'NEILL, J.; CARDENAS, V.A.; AND MEYERHOFF, D.J. Effects of abstinence on the brain: Quantitative magnetic resonance imaging and magnetic resonance spectroscopic imaging in chronic alcohol abuse. Alcoholism: Clinical and Experimental Research 25:1673-1682, 2001. PMID: 11707642

OSCAR-BERMAN, M., AND MARINKOVIC, K. Alcohol: Effects on neurobehavioral functions and the brain. Neuropsychology Review 17:239-257, 2007. PMID: 17874302

PFEFFERBAUM, A., AND SULLIVAN, E.V. Microstructural but not macrostructural disruption of white matter in women with chronic alcoholism. NeuroImage 15:708-718, 2002. PMID: 11848714

PFEFFERBAUM, A.; ROSENBLOOM, M.J.; AND SULLIVAN, E.V. Alcoholism and AIDS: Magnetic resonance imaging approaches for detecting interactive neuropathology. Alcoholism: Clinical and Experimental Research 26:1031-1046, 2002. PMID: 12170114

PFEFFERBAUM, A.; ADALSTEINSSON, E.; AND SULLIVAN, E.V. Cortical NAA deficits in HIV infection without dementia: Influence of alcoholism comorbidity. Neuropsychopharmacology 30:1392-1399, 2005. PMID: 15812566

PFEFFERBAUM, A.; ADALSTEINSSON, E.; AND SULLIVAN, E.V. Dysmorphology and microstructural degradation of the corpus callosum: Interaction of age and alcoholism. Neurobiology of Aging 27:994-1009, 2006a. PMID: 15964101

PFEFFERBAUM, A.; ADALSTEINSSON, E.; AND SULLIVAN, E.V. Supratentorial profile of white matter microstructural integrity in recovering alcoholic men and women. Biological Psychiatry 59:364-372, 2006b. PMID: 16125148

PFEFFERBAUM, A., LIM, K.O.; ZIPURSKY, R.B.; ET AL. Brain gray and white matter volume loss accelerates with aging in chronic alcoholics: A quantitative MRI study. Alcoholism: Clinical and Experimental Research 16:1078-1089, 1992. PMID: 1471762

PFEFFERBAUM, A.; ROSENBLOOM, M.J.; ADALSTEINSSON, E.; AND SULLIVAN, E.V. Diffusion tensor imaging with quantitative fiber tracking in HIV infection and alcoholism comorbidity: Synergistic white matter damage. Brain 130(Pt 1):48-64, 2007. PMID: 16959813

PFEFFERBAUM, A.; ROSENBLOOM, M.J.; DESHMUKH, A.; AND SULLIVAN, E.V. Sex differences in the effects of alcohol on brain structure. American Journal of Psychiatry 158:188-197, 2001. PMID: 11156800

PFEFFERBAUM, A.; ROSENBLOOM, M.J.; ROHLFING, T.; ET AL. Contribution of alcoholism to brain dysmorphology in HIV infection: Effects on the ventricles and corpus callosum. NeuroImage 33:239-251, 2006c. PMID: 16877010

PFEFFERBAUM, A.; ROSENBLOOM, M.J.; ROHLFING, T.; ET AL. Frontostriatal fiber bundle compromise in HIV infection without dementia. AIDS 23: 1977-1985, 2009a, PMID: 19730350.

PFEFFERBAUM, A.; ROSENBLOOM, M.J.; ROHLFING, T.; AND SULLIVAN, E.V. Degradation of association and projection white matter systems in alcoholism detected with quantitative fiber tracking. Biological Psychiatry 65:680-690, 2009b. PMID: 19103436

PFEFFERBAUM, A.; SULLIVAN, E.V.; MATHALON, D.H.; AND LIM, K.O. Frontal lobe volume loss observed with magnetic resonance imaging in older chronic alcoholics. Alcoholism: Clinical and Experimental Research 21:521-529, 1997. PMID: 9161613

PFEFFERBAUM, A.; SULLIVAN, E.V.; MATHALON, D.H.; ET AL. Longitudinal changes in magnetic resonance imaging brain volumes in abstinent and relapsed alcoholics. Alcoholism: Clinical and Experimental Research 19:1177-1191, 1995. PMID: 8561288

PFEFFERBAUM, A., SULLIVAN, E.V.; ROSENBLOOM, M.J.; ET AL. A controlled study of cortical gray matter and ventricular changes in alcoholic men over a five year interval. Archives of General Psychiatry 55:905-912, 1998. PMID: 9783561

ROSENBLOOM, M.J., AND PFEFFERBAUM, A. Magnetic resonance imaging of the living brain: Evidence for brain degeneration among alcoholics and recovery with abstinence. Alcohol Research & Health 31:362-376, 2008.

ROSENBLOOM, M.J.; ROHLFING, T.; O'REILLEY, A.W.; ET AL. Improvement in memory and static balance with abstinence in alcoholic men and women: Selective relations with changes in regional ventricular volumes. Psychiatry Research 155:91-102, 2007a. PMID: 17407808

ROSENBLOOM, M.J.; SULLIVAN, E.V.; SASSOON, S.A.; ET AL. Alcoholism, HIV infection and their comorbidity: Factors affecting self-rated health-related quality of life. Journal of Studies on Alcohol and Drugs 68:115-125, 2007b. PMID: 17149525

ROTHLIND, J.C.; GREENFIELD, T.M.; BRUCE, A.V.; ET AL. Heavy alcohol consumption in individuals with HIV infection: Effects on neuropsychological performance. Journal of the International Neuropsychological Society 11:70-83, 2005. PMID: 15686610

SASSOON, S.A.; FAMA, R.; ROSENBLOOM, M.J.; ET AL. Component cognitive and motor processes of the Digit Symbol Test: Differential deficits in alcoholism, HIV infection and their comorbidity. Acohoiism: Clinical and Experimental Research 31:1315-1324, 2007. PMID: 17550370

SCHULTE, T.; MOLLER-OEHRING, E.M.; JAVITZ, H.; ET AL. Callosal compromise differentially affects conflict processing and attentional allocation in alcoholism, HIV infection, and their comorbidity. Brain Imaging and Behavior 2:27-38, 2008. PMID: 19360136

STEBBINS, G.T.; SMITH, C.A.; BARTT, R.E.; ET AL. HIV-associated alterations in normal-appearing white matter: A voxel-wise diffusion tensor imaging study. Journal of Acquired Immune Deficiency Syndromes 46:564-573, 2007. PMID: 18193498

STOUT, J. C.; ELLIS, R. J.; JERNIGAN, T. L.; ET AL. Progressive cerebral volume loss in human immunodeficiency virus infection: A longitudinal volumetric magnetic resonance imaging study. Archives of Neurology 55:161-168, 1998. PMID: 9482357

SULLIVAN, E.V. Human brain vulnerability to alcoholism: Evidence from neuro-imaging studies. In: Noronha, A.; Eckardt, M.; and Warren, K., Eds. Review of NIAAA's Neuroscience and Behavioral Research Portfolio, NIAAA Research Monograph No. 34. Bethesda, MD: National Institutes of Health, 2000, pp. 473-508.

SULLIVAN, E.V., AND PFEFFERBAUM, A. Neuroimaging of the Wernicke Korsakoff Syndrome. Alcohol and Alcoholism 44:155-165, 2009. PMID: 19066199

THOMPSON, P.M.; DUTTON, R.A.; HAYASHI, K.M.; ET AL. 3D mapping of ventricular and corpus callosum abnormalities in HIV/AIDS. NeuroImage 31:12-23, 2006. PMID: 16427319

THOMPSON, P.M.; DUTTON, R.A.; HAYASHI, K.M.; ET AL. Thinning of the cerebral cortex visualized in HIV/AIDS reflects CD4+ T lymphocyte decline. Proceedings of the National Academy of Sciences of the United States of America 102:15647-15652, 2005. PMID: 16227428

Margaret J. Rosenbloom, M.A., is a research scientist with appointments in the Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, Stanford, California, and the Neuroscience Program, SRI International, Menlo Park, California.

Edith V. Sullivan, Ph.D., is a professor in the Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, Stanford, California.

Adolf Pfefferbaum, M.D, is a professor emeritus in the Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, Stanford, California, and director of the Neuroscience Program, SRI International, Menlo Park, California.

Margaret J. Rosenbloom, M.A., Edith V. Sullivan, Ph.D., and Adolf Pfefferbaum, M.D.

Margaret J. Rosenbloom, M.A., Edith V. Sullivan, Ph.D., and Adolf Pfefferbaum, M.D.


Several noninvasive technologies can be used to study the structure and function of the living brain. Some of these tools are based on the concept of magnetic resonance (MR)--the observation that positively charged particles (i.e., protons) in certain atoms can be detected by placing the tissues containing these atoms in a magnetic field and recording the results. There are several MR-based technologies available, including MR imaging (MRI), diffusion tensor imaging (DTI), and MR spectroscopy (MRS) (More detailed overviews of these methods have been provided by Adalsteinsson et al. 2002; Bigler 1996; Meyerhoff 2001; Rosenbloom and Pfefferbaum 2008.)

MRI detects protons in hydrogen atoms contained in water and fat, two of the most common components of the body. Protons behave differently whether they are incorporated in water molecules or in fat molecules, and these differences can be visualized as differences in intensity on the MRI. Accordingly, tissues with high water content have a different image intensity compared with tissues with a high fat content. These image intensity differences can be used to determine the size, shape, and tissue composition (i.e., gray matter versus white matter) of the brain and thus allow for visualization of gross (i.e., macrostructural) brain neuroanatomy.

DTI makes use of the fact that the water molecules in the brain always are moving, a process known as diffusion. When water molecules are unconstrained by any barriers (e.g., cell membranes), they can move freely in all directions; this movement is random and called isotropic. In tissue with a regular microstructure, such as brain white matter, however, the movement of the water molecules is constrained and follows the orientation of organized microstructure. This movement is called anisotropic. The degree of anisotropy (i.e., fractional anisotropy) and, conversely, of freedom of movement (i.e., diffusivity) can be measured and visualized to determine white matter microstructure. Thus, high fractional anisotropy and low diffusivity, with certain exceptions, reflect healthy white matter.

MRS is based on similar principles as MRI but measures the levels of different metabolites in body tissues rather than the distribution of water and fat. Thus, MRS provides biochemical rather than structural information about brain tissue. Moreover, the results of an MRS analysis are not presented as an anatomical image of brain tissue but as a spectrum with peaks (i.e., magnetic resonances of selective chemicals) indicating the identity and amount of neurotransmitters and neurometabolites detected. Differences in these peaks measured in patients and controls can indicate abnormalities in the metabolism of the cells studied.

MARGARET J. ROSENBLOOM, M.A., is a research scientist with appointments in the Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, Stanford, California, and the Neuroscience Program, SRI International, Menlo Park, California.

EDITH V. SULLIVAN, PH.D., is a professor in the Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, Stanford, California.

ADOLF PFEFFERBAUM, M.D., is a professor emeritus in the Department of Psychiatry & Behavioral Sciences, Stanford University School of Medicine, Stanford, California, and director of the Neuroscience Program, SRI International, Menlo Park, California.
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