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Objective: The induction of long interval cortical inhibition (LICI) in motor cortex with paired pulse transcranial magnetic stimulation (ppTMS) is an established paradigm for the assessment of cortical inhibition, proposed to be related to GABA(B) receptor inhibitory neurotransmission. This study aimed to further evaluate recent methods of the assessment of LICI in non motor regions with ppTMS and electroencephalography (EEG)., Methods: ppTMS was applied using a single coil to the motor and dorsolateral prefrontal cortex (DLPFC) in 14 healthy subjects, and in the parietal lobe in 5 of those subjects., Results: In the motor cortex, LICI resulted in significant suppression in mean cortical evoked activity on EEG between 75 and 250 ms following delivery of the test stimulus. Maximal inhibition was seen from 50 to 250 ms in DLPFC, and between 50 and 175 ms in the parietal lobe., Conclusions: ppTMS may be used to produce LICI in several cortical regions with a time course similar to known GABA(B) activity., Significance: ppTMS induction of LICI can be recorded by combining TMS with EEG and seems to relate to GABA(B) activity.

Imaging studies of schizophrenia (SCZ) have repeatedly demonstrated volume differences in superior temporal gyrus (STG) and its subregions. Among them, some studies employed the Region of Interest (ROI) method. We carried out a systematic review of the published literature on STG volumetry MRI studies to examine the potential of ROI method for identifying specific structural differences and correlations with clinical variables including hallucinations and thought disorder symptoms in SCZ. Forty-six studies were identified as suitable for review and analysis including 1444 patients with SCZ and 1327 controls. Female and left-handed subjects are under-represented in the literature and insight from sex and handedness differences may be lost. Thirty-five studies reported significant differences in STG or subregional volumes including bilateral or unilateral ROI, and volume reduction was the most common change in SCZ. Thirty studies reported correlations between volume changes and clinical symptoms or syndromes and 18 found positive results. Among them, left STG or subregions appear to be more involved in the generation of hallucinations and thought disorder than right side. The majority of five follow-up studies found evidence of progressive changes in volumes. Clinical heterogeneity, MRI acquisition parameters, anatomical landmarks for ROI, and sample characteristics, are likely to be the main factors leading to heterogeneous results. Clearly this research links pathophysiological changes in the STG with the development of hallucinations and thought disorder in patients with SCZ, especially in the left side. There is a suggestion that these changes may be progressive but this requires more thorough and comprehensive assessment.

The aim of this study is to investigate whether repetitive transcranial magnetic stimulation (rTMS) targeted to a specific site in the dorsolateral prefrontal cortex (DLPFC), with a neuro-navigational method based on structural MRI, would be more effective than rTMS applied using the standard localization technique. Fifty-one patients with treatment-resistant depression were randomized to receive a 3-week course (with a potential 1-week extension) of high-frequency (10 Hz) left-sided rTMS. Thirty trains (5 s duration) were applied daily 5 days per week at 100% of the resting motor threshold. Treatment was targeted with either the standard 5 cm technique (n=27) or using a neuro-navigational approach (n=24). This involved localizing the scalp location that corresponds to a specific site at the junction of Brodmann areas 46 and 9 in the DLPFC based on each individual subject's MRI scan. There was an overall significant reduction in the Montgomery-Asberg Depression Rating Scale scores over the course of the trial, and a better outcome in the targeted group compared with the standard localization group at 4 weeks (p=0.02). Significant differences were also found on secondary outcome variables. The use of neuro-navigational methods to target a specific DLPFC site appears to enhance response to rTMS treatment in depression. Further research is required to confirm this in larger samples, or to establish whether an alternate method based on surface anatomy, including measurement from motor cortex, can be substituted for the standard 5 cm method.

The caudate nucleus is a structure implicated in the neural circuitry of psychological responses to trauma. This study aimed to quantify the volume of the caudate in persons exposed to trauma. Thirty-six subjects under 65 were recruited from transport workers in Stockholm who reported having been unintentionally responsible for a person-under-the-train accident or among employees having experienced an assault in their work (1999-2001) between 3 months and 6 years before MRI scanning. In those exposed to the trauma, a DSM-IV diagnosis of post-traumatic stress disorder (PTSD) was made by an independent psychiatrist, with subjects being classified as PTSD or no PTSD. MRI data were analyzed blindly to all clinical information by an experienced rater using a standardized manual tracing protocol to quantify the volume of the caudate. Within-group comparisons of PTSD (n=19) and no PTSD (n=17) found the right caudate nucleus to be significantly (9%) larger than the left: a right hemisphere baseline asymmetry. A multivariate analysis of covariance (MANCOVA) was conducted to assess the volume of the caudate nucleus (right and left) in relation to the diagnosis of no PTSD (n=17) or PTSD (n=19). After adjustment for the covariates (age, sex, intracranial volume, years since trauma, and number of trauma episodes), there was a significant difference in raw right caudate nucleus volume between subjects with PTSD compared with those without PTSD. Volume of the left caudate nucleus was not significantly different between the PTSD and no PTSD groups. The right caudate volume in the PTSD group was 9% greater compared with the no PTSD group. There is a larger right hemisphere volume of the caudate within those exposed to trauma with active PTSD compared with those without PTSD, superimposed upon a baseline caudate asymmetry.

Several studies have demonstrated that cortical inhibition (CI) can be recorded by paired transcranial magnetic stimulation (TMS) of the motor cortex and recorded by surface electromyography (EMG). However, recording CI from other cortical regions that are more closely associated with the pathophysiology of some neurological and psychiatric disorders (eg, dorsolateral prefrontal cortex (DLPFC) in schizophrenia) was previously unattainable. This study, therefore, was designed to investigate whether CI could be measured directly from the motor cortex and DLPFC by combining TMS with electroencephalography (EEG). Long-interval CI (LICI) is a TMS paradigm that was used to index CI in the motor cortex and DLPFC in healthy subjects. In the motor cortex, LICI resulted in significant suppression (32.8+/-30.5%) of mean cortical evoked activity on EEG, which was strongly correlated with LICI recorded by EMG. In the DLPFC, LICI resulted in significant suppression (30.1+/-26.9%) of mean cortical evoked activity and also correlated with LICI in the motor cortex. These data suggest that CI can be recorded by combining TMS with EEG and may facilitate future research attempting to ascertain the role of CI in the pathophysiology of several neurological and psychiatric disorders.

The fields of personality research and neuropsychology have developed with very little overlap. Gray and McNaughton were among the first to recognize that personality traits must have neurobiological correlates and developed models relating personality factors to brain structures. Of particular note was their description of associations between conditioning, inhibition and activation of behaviours, and specific neural structures such as the hippocampus, amygdala and the prefrontal cortex. The aim of this study was to determine whether personality constructs representing the behavioural inhibition and activation systems (BIS/BAS) were associated with volumetric measures of the hippocampus and amygdala in humans. Amygdalar and hippocampal volumes were measured in 430 brain scans of cognitively intact community-based volunteers. Linear associations between brain volumes and the BIS/BAS measures were assessed using multiple regression, controlling for age, sex, education, intra-cranial and total brain volume. Results showed that hippocampal volumes were positively associated with BIS sensitivity and to a lesser extent with BAS sensitivity. No association was found between amygdalar volume and either the BIS or BAS. These findings add support to the model of Gray and McNaughton, which proposes a role of the hippocampus in the regulation of defensive/approach behaviours and trait anxiety but suggest an absence of associations between amygdala volume and BIS/BAS measures.

Despite a growing interest in this area, we continue to lack an understanding of the pathophysiology of depression and of treatment-resistant depression (TRD) in particular. The role of the medial temporal lobe, particularly the hippocampus, has been widely implicated in the aetiology of depression. However, related structures such as the entorhinal cortex have not been systematically examined. This research study aimed to examine possible abnormalities in the volume of the entorhinal cortex (ERC) in TRD patients. A group of 45 TRD patients and 30 healthy age- and sex-matched controls underwent magnetic resonance imaging (MRI). ERC volumes were manually traced from MRI data using ANALYZE software. An analysis of variance was conducted between subject groups and in the sexes separately while controlling for the effects of brain size via intracranial volume (ICV). Results revealed significant reductions in the volume of the left ERC of female patients. Although preliminary, our findings suggest that anatomical abnormalities in the ERC may confer vulnerability to treatment resistance. Confirmatory longitudinal studies are required to determine whether these abnormalities predate the onset of depression or are the result of a more chronic, treatment-resistant course of illness.

A number of studies using paired pulse transcranial magnetic stimulation (TMS) have demonstrated that cortical inhibition (CI) of the motor cortex can be recorded and also gauged through surface electromyography. However, recording CI from other brain regions that are more directly related with the pathophysiology of some neurologic and psychiatric disorders (e.g., dorsolateral prefrontal cortex (DLPFC) in schizophrenia) was previously fraught with technical difficulties. This study was therefore designed to examine, through a combination of TMS with EEG, whether CI could be measured directly from the motor cortex, DLPFC, and another non-motor region. To index CI, long interval cortical inhibition (LICI; a TMS paradigm) was used in the motor cortex and DLPFC in 14 healthy subjects, and in the parietal lobe in 5 of those subjects. In the motor cortex, LICI resulted in a significant suppression in mean cortical evoked activity on EEG (37.31 +/- 47.51%). In the DLPFC, LICI resulted in a significant suppression (32.45 +/- 47.86%) in mean cortical evoked activity and did not correlate with LICI in the motor cortex although they did not significantly differ. In the parietal lobe, LICI resulted in significant suppression (47.76 +/- 44.70%) in mean cortical evoked activity. In conclusion, CI in the dorsolateral prefrontal cortex, motor cortex and parietal cortex were similar at 120% of motor threshold. These data suggest that CI can be recorded by combining TMS with EEG and may facilitate future research attempting to ascertain the role of CI in the pathophysiology of several neurologic and psychiatric disorders.

Background: The APOE*E4 allele has been associated with greater gray matter atrophy and with Alzheimer's disease. The aim of this study was to investigate whether the relationship between cerebral gray matter atrophy and APOE*E4 genotype was also present in a community-dwelling, nondemented 60- to 64-year-old cohort., Methods: Hippocampal and amygdalar volumes were manually traced and analyzed on 331 cranial T1-weighted magnetic resonance imaging (MRI) scans to detect differences associated with APOE*E4 genotype. Voxel-based morphometric (VBM) analyses were applied to detect regional gray matter volume differences., Results: No total, hippocampal, or amygdalar gray matter volume difference was detected between APOE*E4 carriers and noncarriers., Conclusions: In nondemented 60- to 64-year-olds, there was no association between APOE genotype and gray matter volume using both region-of-interest analysis and VBM.

Reduced volumes of the hippocampus (HC) and amygdala (AG) are potential biomarkers for Alzheimer's disease (AD) and other neuropsychiatric disorders. Published studies on HC and AG volumes suffer from methodological limitations, and a valid and reliable normative database does not exist. This study aimed to establish a database of HC and AG volumes from a large community sample of participants 60-64 years old and relate them to cognition. A total of 452 randomly selected participants (from 622 approached) were retained in the study (238 males, 214 females), and all received brain MRI scans, as well as cognitive and physical assessments. HC and AG volumes were estimated from manual tracings on T1-weighted images, and intracranial volume (ICV) was obtained from an automated program. In both sexes, right hippocampi were larger than left, while left amygdala were larger than right. The only correlation to remain significant after normalization was left HC volume and percent retention of a word list in females. This study provides a HC and AG volumetrics database and describes its relationship with cognitive performance in a representative sample using a standard methodology that will be a reference for future studies. It will therefore have clinical applicability in early AD and other disorders.

Studies of patients with major depression disorder (MDD) have revealed reduced hippocampal volumes, but findings have been inconsistent due to sample and measurement differences. The current study sought to measure this structure in a large sample of MDD and control subjects, using a strict measurement protocol, in order to elucidate morphological-specific volumetric differences. Forty-five subjects with treatment-resistant MDD and 26 controls underwent psychiatric assessments and brain magnetic resonance imaging (MRI). The findings of this study indicate that (1) MDD results in reduced hippocampal volume, particularly in the tail section, (2) region of interest (ROI) estimation protocols and sample characteristics may help explain volumetric differences between previous MDD studies, and (3) specific ROI atrophy in treatment-resistant depression is influenced by sex.

Published normative volumetrics of the hippocampus (HC) vary substantially. While the protocol suggested by Watson et al. (Neurology 42 (1992) 1743-1750; Arch Neurology 54 (1997) 1521-1531) is the most frequently adhered to, this leaves the posterior section of the HC tail unmeasured, which has been estimated to be in the order of 2-4 mm, representing 5-10% of total HC volume. The objective of the current study was to compare HC volumes according to the method of Watson et al. (Neurology 42 (1992) 1743-1750; Arch Neurology 54 (1997) 1521-1531) against those measured to include the posterior tail section. From a random community sample of 60-64 yr old individuals, 478 subjects underwent magnetic resonance imaging brain scans. Of these, 452 scans (238 males and 214 females) were adequate for hippocampal measurement. The scans comprised whole brain T1- weighted and T2-weighted FLAIR images. One hundred and fifty scans were randomly selected for the measurement of HC volumes beyond the opening of the crus of the fornix by manual tracings on T1-weighted images by a trained operator. Intracranial volume (ICV) and total brain volume (TBV) were measured using an automated program. We found that the posterior HC tail extended for a mean of just over 5 mm and comprised 11% of total HC volume. Males had significantly larger raw HC volumes, and while normalization with ICV or TBV reversed this pattern, it was significant only when the posterior HC tail was included in the measurement. In conclusion, this study showed that including the posterior part of the tail can influence the results of HC measurement. An argument is presented that accurate HC volumes should include the entire HC and not exclude the tail., (Copyright 2005 Wiley-Liss, Inc.)

We evaluated the association between handedness and manual tracings of hippocampal and amygdalar volumes. Brain MRI and handedness data were obtained for 441 community dwelling participants aged 60-64 years of whom 31 were left-handed. Both absolute and normalized hippocampal volumes were larger in left-handed women than right-handed women. Hippocampal volume was not associated with handedness in men, and amygdalar volume was not associated with handedness in men or women. There was no right-left asymmetry in hippocampal or amygdalar volumes in either gender. We conclude that volumetric differences by handedness must be taken into account where hippocampal volumes are of clinical importance. Our results may also explain reports of lower rates of dementia in left-handed individuals.

We review nineteen empirical studies of mild cognitive impairment (MCI), age-associated memory impairment (AAMI) and related classifications reporting volumetric data on the hippocampus, entorhinal cortex and amygdala. Studies varied considerably in terms of the selection of participants, sample characteristics, the definitions of regions of interest and normalization techniques. Effect sizes for differences in left hippocampal volume and right hippocampal volumes of AAMI, MCI and pre-clinical dementia groups compared with controls ranged from 0.47 to 1.34. Effect sizes for left and right hippocampal volumes for Alzheimer's disease (AD) versus control were 1.88 and 1.75 respectively. Longitudinal results confirm that initial hippocampal volume is predictive of conversion to AD. Greater standardization in methodology and the development of normative age-referenced databases of regional brain volumes is required.

Personal computers may be used to create, store, and deliver graphical presentations. With computer-generated combinations of the five media (text, images, sound, video, and animation)--that is, multimedia presentations--the effectiveness of message delivery can be greatly increased. The basic tools are (1) a personal computer; (2) presentation software; and (3) a projector to enlarge the monitor images for audience viewing. Use of this new method has grown rapidly in the business-conference world, but has yet to gain widespread acceptance at medical meetings. We review herein the rationale for multimedia presentations in medicine (vis-à-vis traditional slide shows) as an improved means for increasing audience attention, comprehension, and retention. The evolution of multimedia is traced from earliest times to the present. The steps involved in making a multimedia presentation are summarized, emphasizing advances in technology that bring the new method within practical reach of busy physicians. Specific attention is given to software, digital image processing, storage devices, and delivery methods. Our development of a urology multimedia presentation--delivered May 4, 1996, before the Society for Urology and Engineering and now Internet-accessible at http://www.usrf.org--was the impetus for this work.