A longitudinal diffusion tensor imaging study in symptomatic Huntington's disease.

OBJECTIVE: The striatum and its projections are thought to be the earliest sites of Huntington's disease (HD) pathology. This study aimed to investigate progression of striatal pathology in symptomatic HD using diffusion tensor imaging. METHOD: Diffusion weighted images were acquired in 18 HD patients and in 17 healthy controls twice, 1 year apart. Mean diffusivity (MD) was calculated in the caudate, putamen, thalamus and corpus callosum, and compared between groups. In addition, caudate width was measured using T1 high resolution images and correlated with caudate MD. Correlation analyses were also performed in HD between caudate/putamen MD and clinical measures. RESULTS: MD was significantly higher in the caudate and putamen bilaterally for patients compared with controls at both time points although there were no significant MD differences in the thalamus or corpus callosum. For both groups, MD did not change significantly in any region from baseline to year 1. There was a significant negative correlation between caudate width and MD in patients at baseline but no correlation between these parameters in controls. There was also a significant negative correlation between Mini-Mental State Examination scores and caudate MD and putamen MD at both time points in HD. CONCLUSIONS: It appears that microstructural changes influence cognitive status in HD. Although MD was significantly higher in HD compared with controls at both time points, there were no longitudinal changes in either group. This finding does not rule out the possibility that MD could be a sensitive biomarker for detecting early change in preclinical HD.

Increased cortical recruitment in Huntington's disease using a Simon task.

Cognitive deficits in Huntington's disease (HD) have been attributed to neuronal degeneration within the striatum; however, postmortem and structural imaging studies have revealed more widespread morphological changes. To examine the impact of HD-related changes in regions outside the striatum, we used functional magnetic resonance imaging (fMRI) in HD to examine brain activation patterns using a Simon task that required a button press response to either congruent or incongruent arrow stimuli. Twenty mild to moderate stage HD patients and 17 healthy controls were scanned using a 3T GE scanner. Data analysis involved the use of statistical parametric mapping software with a random effects analysis model to investigate group differences brain activation patterns compared to baseline. HD patients recruited frontal and parietal cortical regions to perform the task, and also showed significantly greater activation, compared to controls, in the caudal anterior cingulate, insula, inferior parietal lobules, superior temporal gyrus bilaterally, right inferior frontal gyrus, right precuneus/superior parietal lobule, left precentral gyrus, and left dorsal premotor cortex. The significantly increased activation in anterior cingulate-frontal-motor-parietal cortex in HD may represent a primary dysfunction due to direct cell loss or damage in cortical regions, and/or a secondary compensatory mechanism of increased cortical recruitment due to primary striatal deficits.

A preliminary fMRI study of the effects on cortical activation of the treatment of refractory auditory hallucinations with rTMS.

Three patients underwent fMRI during a word generation task before and after successful treatment of auditory hallucinations with rTMS and were compared to four control subjects. There was a significant increase and more normal task related brain activation in brain areas involved in language processing including left temporoparietal cortex after rTMS treatment.

EEG coherence measures during auditory hallucinations in schizophrenia.

We studied the change in EEG alpha-band average coherence between auditory hallucination (AH) and non-auditory hallucination (non-AH) states in seven auditory hallucinating schizophrenia patients. Four cortical regions were considered based on the existing dominant models for auditory hallucinations, the inner speech model and the central auditory processing deficit (CAPD) model. Coherences between electrodes located over Broca's area (BA 44/45) and Wernicke's area (BA 22/42) and between electrodes located over left-right temporal cortices were examined. There was no significant change observed in the coherence between Broca's and Wernicke's areas, but a significant increase was observed in coherence between the left and right superior temporal cortices during AHs compared with non-AHs, suggesting increased bilateral coherence between auditory cortical areas. Since coherence is a pairwise measure of functional correlation between regions, our findings suggest abnormally increased synchrony between the left and right auditory cortices during AHs in schizophrenia. Further, a significant increase in relative power was observed in the left, but not in the right auditory cortex during AHs. Thus our findings support the CAPD model and are consistent with that which postulate reduced prosodic processing during AHs.

Diffusion tensor imaging in Huntington's disease reveals distinct patterns of white matter degeneration associated with motor and cognitive deficits.

White matter (WM) degeneration is an important feature of Huntington's disease (HD) neuropathology. To investigate WM degeneration we used Diffusion Tensor Imaging and Tract-Based Spatial Statistics to compare Fractional Anisotropy, Mean Diffusivity (MD), parallel diffusivity and perpendicular diffusivity (λ⊥) in WM throughout the whole brain in 17 clinically diagnosed HD patients and 16 matched controls. Significant WM diffusivity abnormalities were identified primarily in the corpus callosum (CC) and external/extreme capsules in HD patients compared to controls. Significant correlations were observed between motor symptoms and MD in the CC body, and between global cognitive impairment and λ⊥ in the CC genu. Probabilistic tractography from these regions revealed degeneration of functionally relevant interhemispheric WM tracts. Our findings suggest that WM degeneration within interhemispheric pathways plays an important role in the deterioration of cognitive and motor function in HD patients, and that improved understanding of WM pathology early in the disease is required.

A functional magnetic resonance imaging study of the effects of low frequency right prefrontal transcranial magnetic stimulation in depression.

The study aimed to explore the biological effects of low-frequency repetitive transcranial magnetic stimulation (LFR-TMS) treatment applied to the right prefrontal cortex, comparing this with the effects of high-frequency left-sided (HFL-TMS) in patients with treatment-resistant depression. Twenty-six patients with treatment-resistant depression were randomized to receive either daily LFR-TMS or HFL-TMS treatment for 3 weeks and underwent functional magnetic resonance imaging during a planning task before and after treatment. Patients responded clinically to both forms of treatment with no difference in the degree of response (F1,24 = 0.65;P > 0.05). Low-frequency repetitive transcranial magnetic stimulation resulted in no overall change in task-related activation. However, responders to LFR-TMS demonstrated a bilateral decrease in activity in middle frontal gyrus. In contrast, HFL-TMS produced an increase in activation in left precuneus with responders showing increased activation in several additional regions. Response to LFR-TMS is associated with a bilateral reduction in frontal activation that does not seem to be a nonspecific effect of treatment and differs from the response to HFL-TMS.